Are you shutting down all non-essential programs (especially anti-virus) before starting the game? Firewalls can cause conflicts (generally on startup or loading screens) and overlays from graphics tweaking/monitoring programs or chat programs can also caused issues.
Can you start the Classic version of the game?
The Definitive Edition is '..\Divinity Original Sin 2\DefEd\bin\EoCApp.exe', while '..\Divinity Original Sin 2\Classic\EoCApp.exe' is the original release.
Try starting the launcher from the '..\Divinity Original Sin 2\bin\SupportTool.exe' executable.
If the launcher doesn't start from the executable, try deleting the config.xml file in the '..\Divinity Original Sin 2\bin' folder, as well as 'C:\Users\<UserName>\AppData\Local\LarianLauncher' (copy and paste %LocalAppData%\LarianLauncher into Windows Explorer to quickly open that folder).
If that doesn't help, try reinstalling .Net Framework 4.
C:\Program Files (x86)\GalaxyClient\Dependencies\__redist
or
https://www.microsoft.com/net/download/dotnet-framework-runtime If that doesn't at least get the launcher starting from the executable, there is also a
Microsoft .NET Framework Repair Tool, or if that doesn't help,
Cleanup Tool.
For the game:
Try verifying local files, if you are using Galaxy: select Divinity: Original Sin 2 in the left column, then click on the More button, and in the Manage menu select 'Verify / Repair'.
If you check the Event Viewer, does that give an error code or 'Faulting Module' file name? It may not, since an error message is coming up.
- click Start (or WinKey-R), then type "event viewer" into the search box. in Windows 10, 'event' should bring up 'View event logs'.
- after starting the Event Viewer, expand 'Windows Logs' in the left column and select 'Application'
- in the center column, look for a recent error for the game (maybe sort by Date and Time, or search for 'EoCApp')
- check the information under the 'General' tab below the list of events, starting with "Faulting application name..."
Check for updated graphics drivers, and Windows updates in general.
Normally, GOG install the redistributable packages with the game, if required, but you can check, and reinstall them manually:
- Visual C++ Redist 2017 (64bit), now included with the 2019 release (if this is a problem, generally there should be an error when starting from the executable, mentioning a VC related dll)
C:\Program Files (x86)\GalaxyClient\Dependencies\__redist
or
https://support.microsoft.com/en-ca/help/2977003/the-latest-supported-visual-c-downloads If you get an error mentioning the api-ms-win-crt-runtime-l1-1-0.dll file, it is part of the Microsoft Universal C Runtime, and on Windows 7 or Windows 8.1 can be downloaded at the link below, or gotten through Windows update (it is already part of Win 10).
https://support.microsoft.com/en-us/kb/2999226 Try exiting out of Galaxy, if applicable, browse to the '..\Documents\Larian Studios' folder and rename the 'Divinity Original Sin 2 Definitive Edition' subfolder.
This folder contains the saved games, configuration files and a level cache folder. Deleting or renaming it will get the game to recreate it on startup; playing the game from a different Windows user account would effectively do the same thing.
Next, extract the replacement folder from
this download into your '..\Documents\Larian Studios' folder, and see if that will let you start the game directly from the executable.
The graphicSettings.lsx file is set to 1280x720 Windowed mode, Very Low quality preset and low audio quality, which you can change in the options (manually, or hit autodetect) if this gets the game to start.
If that works, create a new profile and maybe check that you can start a new game and save/load. If you have any DE saves that you want to keep, exit and copy a couple saves from the renamed folder into the newly created profile's ..\Savegames\Story folder. If that continues to let you start the game and load the saves, move the rest of the saves over.
If the game still gives that error, delete the replacement My Documents D:OS 2 DE folder and rename the original back again.
Try doing a clean boot and then test the game. Click Start, or hit WinKey-R, type in msconfig and hit enter; in the General tab, click Selective Startup, uncheck Load startup items (if required) and leave Load system services and Use original boot configuration options checked. Next, click on the Services tab, check the box to Hide all Microsoft services, then click the Disable All button (maybe make a note of which are currently enabled/disabled), then click OK and reboot the computer.
Run msconfig again to switch back to the normal boot configuration.
If that doesn't help, please email supportdos2@larian.com with a dxdiag report (WinKey-R, type in dxdiag and hit enter, then when it finishes loading click on the 'Save All Information...' button and save the report somewhere handy). Also check the '..\Divinity Original Sin 2\DefEd\bin' folder for the gold.log file, and if there are any 'CrashDump' files being created, zip a few together to include.