Okay, this is the relevant part of your post for troubleshooting.

Assuming the manufacturer of the board was the same as well, then you shouldn't need to reinstall windows in most cases for replacing a like-for-like board and putting in even a different chipset, however it can be recommended from a troubleshooting perspective.

Can you clarify if enabling secure boot makes the game work as normal. The above quote suggests it works, your comment in the below quote suggests it doesn't:

If secure boot allows you to run the game, just leave it enabled (troubleshooting completed)

If it still doesn't work, MysterD may be on to something. I'd disable the iGPU in your BIOS if you haven't already done so. While it won't impact on power consumption or anything like that, turning it off will reduce the chance that you're getting a conflict between the real GPU and the onboard.

Hello? On secure boot my entire GPU is disabled and the game runs on 1 FPS because the whole game is basically processed by the CPU only and the integrated GPU is disabled by BIOS... system can not use it.

If i enable any more than the raw minimum, Dishonored 2 will not run anymore.

This is NOT a solution... end of story.

A fully "unlocked" desktop 3090 TI, with very high quality parts attached, the industrys most expensive-controller (just a few high end GPUs got it), does not break a sweat on the hardware side and stays stable far beyond 400 W of power draw (it usually never happens). And the PSU is a Seasonic Titanium.. everything breaks sooner than this. I love quality but there is still lot of hassles with enough of bad luck and the industrys incompetence.

I fully agree... this game generally does not enjoy any AMD hardware, yet i got no Adrenaline because no AMD GPU (never used one on this OS). Yet i do not think the 7800 X3D is a issue, but the alien-like-AMD-motherboard can be problematic for this game.

Are you sure that you aren't confusing "Secure Boot"
https://learn.microsoft.com/en-us/windows-hardware/design/device-experiences/oem-secure-boot
with "Safe Mode"?
https://support.microsoft.com/en-us/windows/start-your-pc-in-safe-mode-in-windows-92c27cff-db89-8644-1ce4-b3e5e56fe234

And btw. if both your GPU and iGPU would be disabled, you wouldn't get 1 FPS - you would get a black screen + BIOS error message.

Well then it is safe mode. I do not need secure boot because i got almost no foreign stuff installed, and if so.... it is 99% other games only.

But of course, in theory even those "other games" may be able to screw up some settings which is enjoyed by Dishonored 2 and it is possible it may fail to run because of the huge collection of other games (conflict issue somewhere).

Removing them is not a option.... so i can only try to make the OS a bit more clean by resetting or reinstalling. No warranty it will work... this is the true hassle here.

It would be highest benefit to me if i know the actual conflict issue of the game. Else... at some point i may have the same issue reappearing...

I dunno if GPU-disabling will solve this, as it could be AMD Adrenaline kicking it in the head; that Adrenaline could be the entire problem; not sure, ain't tested it.

So, I remember say NVidia Geforce Nvidia Experience program (I think it was NVCont) used to cause all kinds of problems w/ boot, crashes, freezes, etc - just w/ that program running in the background with say Deus Ex: Invisible War. So, who knows? Anything's possible. [shrug]

We also know Dis 2 is a DX11 and DX11.1 game.

Other ideas - my last resort idea. What about say running Dis 2 with say a DX emulator or DX-wrapper? We know some games need wrappers to work b/c God knows what changes Nvidia, Microsoft, or AMD might've made to mess stuff up in DirectX itself, GPU's Drivers, Additional Software for their GPU's, whatever. Sometimes, DX Emulators/Wrappers can fix that mess. So, what about say using DGVoodoo2? Or DXWnd? or DXVK OG or DXVK A-Sync?

Again, just ideas - ain't tested this yet, as I don't have Dis 2 on me here to install; not at home right now to grab it and just install it and then experiment.

EDIT - As anyone tried Dishonored 2 Steam or GOG versions on say Linux or Steam Deck? What about Dis 2 Steam or GOG version on say ROG Ally on W11 over there?

If you have AMD drivers installed, remove them.
https://www.guru3d.com/files-details/display-driver-uninstaller-download.html

Okay, this is why clarity and using the right names for things is important.

If it's loading in Safe Mode, this does give some weight to the idea that there's a driver issue causing the problem - I'm not sure how it works in Windows 10, but I'd imagine that there's a generic VGA adapter that it's using in Safe Mode that gives basic Direct3D functionality.

I'm not going to put too much more time into this as the language/communication barrier is making this more of a struggle than I'd like, but my final recommendations (other than trying what others on the thread suggest) would be (in whatever order you want) No guarantees that any of these will work.

1. Try disabling system devices to see whether something is conflicting with the game in question. You can disable through Device Manager or physically remove them - also remove the drivers when you do this.

2. Try clean installing GPU drivers

3. Try a different GPU - or try activating your integrated GPU, remove the nVidia card, uninstall nVidia drivers and see if it works then. This will help you isolate where in your system your problem is.

4. Clean off any old drivers

5. Clean install Windows 10 (or clean install Windows 11; with a newish CPU and chipset you might have better luck with Windows 11 drivers). Clean installs delete all data and settings - so back anything up before you do this.

6. Contact support - if you bought the game from here, I believe GoG offers support in German and French, so assuming either of those is your native language you may find it easier to get the problem resolved in that language.

I'd love to see GOG fix Dis 2 and work their magic.

Though, this really seems like something programmers & technical guys at Arkane should really fix themselves and issue a new patch to Steam, Epic, GOG, Xbox for PC, and anywhere else.

Though, like 70% of their studio left by Redfall's completion and b/c of that game, so....I dunno. [shrug]

EDIT:
Oh, does anyone know is Dishonored: Death of the Outsider (i.e. Dishonored 2's stand-alone expansion that's also on VOID Engine) has these problems too?

Sorry this is not going to help you, but maybe at least help you feel a bit more miserable.

I just installed Dishonored 2 (GOG offline installer) on my Lenovo Legion Pro 5 gaming laptop, and it runs great without any issues. Getting good framerates as well.

AMD Ryzen 9 5900HX CPU ("with Radeon Graphics")
NVidia Geforce RTX 3080 Laptop GPU
32GB RAM
Windows 11 Home

I am now resetting my OS with very unknown results and very huge work. This is not a light and easy procedure such as some people may suggest, at least not with my amount of data. There can be something screwing up on this whole process.. license not accepted anymore and way more stuff. So i take a huge risk here but i hope it will work out somehow. It will take a lot of time even "Just to install the OS", this is no light procedure... it is a "reinstall".

In between there was even some sort of "freeze", this is just creepy. I generally do not recommend this if the issue is not very critical, for example blue screen or whatelse... but i never had any bluescreen or other instability issues, the stuff i do is "overkill".

Depends what the actual problem is and how common the problems are. For me all the three games seem to work fine, just tried them, even though my system should have several red flags, like I am using a laptop with two graphics processors, AMD Ryzen CPU, an external monitor etc. (that according to some articles were problems for this game?).

This reminds me of this Shadow Warrior 2 problem that me and many others seemed to be having, and the solution was quite obscure:

https://www.gog.com/forum/shadow_warrior_series/the_game_freezes_at_the_sword/post4

So who knows what setting or thingie may be causing those problems, and why some are not getting them. I was kinda expecting to run into problems as I have a laptop with two different graphics chipsets etc... but no.

Steam Deck got a custom OS (Steam OS Version 3) which is mostly adapted to those games located on Steam. Sure, it never works perfect but if you have such a strong force such as Steam "behind" then the most well known games, including "Dishonored 2" are surely tuned in order to get it to work using it.

I rather fear the "lonely" Dishonored 2 versions somewhere else with much lesser dev support (no matter official dev or Steam dev)... those got a higher issue for being unable to work at some point; unless users are patching it.

To late already because i am done resetting my PC, now i installed the mainboard-drivers (including chipset) and the device manager looks proper to me (no conflict or other issues). GPU driver i was installing the newest one too. Now Dishonored 2 is in fact running now... i was not removing my old installed files and so far it looks like it is working.

But.... i will only smile if everything has been sufficiently tested... this is the lesson i had to learn "the hard way". As long as not everything is verified and running, i am not done.

Cyberpunk was successfully booted up too... so i guess i am pretty safe, those 2 games are the most problematic or unstable ones in my experience.

I think, to be honest: 99% of the stuff out there might have some grain of truth inside, as there is rarely a "complete lie"... rather a mix between truth and lies. However, i think Dishonored 2 is not a game that will fail to run because of "a single thing, such as "Hybrid GPU" or whatelse.... it is simply a game which will react very cranky as soon as to much "small bad factors" are being added to the "list of bad things". So, the users may find countless reasons, but not any reason is wrong by its own... instead it is the "summary" of many of those reasons.... and at some point a "rather dodgy or unstable engine" simply will stop to work... kinda like "the straw that breaks the camels back". It is almost same for Cyberpunk with a comparable behaviour...

While, the big "park" of games are not sensitive to such issues as they are more "self reliant" with lesser risk of having a summary of bad config "breaking their back".., which is indeed wise.

Of course the installed files (other games) was never installed on my OS drive, instead "the menu-entrys" only, along with install infos for uninstalling. The games was always installed on separate "gaming drives", which should help if such issues are appearing (easyer having the issue isolated).