I have looked at Keytweak, which I think would work, but requires a PC reboot each time as it alters the registry which is a major pain. I tried AutoHotKey which works in Windows environment, but when in game, it has no effect.

(my use-case is for rebinding keys for comfort, not cheating!)

Thanks
Oblaram the Carpal Tunnel Sorcerer

Hey yoxxy104, what kind of rebinding are you looking to do. We could make this a feature in DevilutionX, or you could compile your own version with custom mapping if you want.
https://github.com/diasurgical/devilutionX/releases

When I played Diablo 2 I used AutoHotKey to disable my windows key and alt-tab function (to avoid minimizing the game and getting killed). I did so by rebinding the keys. My point is it worked in D2 so I'm not sure why it would not work in D1.
You might want to test it for other games and double check your script to make sure it's functioning correctly. You might try adding this line to the top of your AHK script:

IfWinExist Diablo

About cheating... And this is going to be subjective but the inability to rebind the keys is part of the game. If you rebind them you are giving yourself an advantage that other players do not have, which could be said to be cheating. Everybody else is stuck using the default keys. You might not see that as cheating but some people will. In E-sport tournaments for example everybody is forced to use default keys to keep things fair.

If he's playing single-player (the only way I play the game) then it hardly matters, eh? Obviously, this isn't E-sports...;)

Whether it matters them is their choice. Like I said it is subjective. They mentioned the subject so i offered a perspective. I was talking about multiplayer games; I thought that was obvious.

Anders - I am wanting to rebind keys to be more adjacent. I have tendonitis and also am left handed and the default mapping is very awkward. Points taken about what is cheating, but it is also an accessibility issue. Also if I were in some competition, I get it. But we are just a bunch of middle aged dudes playing an old video game. I hardly think remapping my keys is going to make any material diffeeence.

Use Autohotkey. Is quite simple and lets you rebind everything.

I can hardly agree with that. To keep things fair it should allow everyone to use their own best setups.

Instead, a default setting for everyone will only make a certain group of players happy yet others uncomfortable. For my perspective that is completely unfair. Can you imagine the Olympic Games requires that all atheletes wear the same size 8 running shoes 'so to keep it fair'?

I know it's been a while, but we have now added the option for rebinding most keys via the ini, hope this helps you:

https://github.com/diasurgical/devilutionX/releases