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.
There is a known conflict with the graphics injector GeDoSaTo, for example (at least in a couple cases just the existence of its shim64.dll file causes a conflict with the Definitive Edition, even if the program was not running).

Try exiting out of the Steam client, and starting the game directly from the '..\SteamApps\common\Divinity Original Sin 2\DefEd\bin\EoCApp.exe' program file, by right clicking and running as administrator (or '..\Divinity Original Sin 2\Classic\EoCApp.exe' for the original release).

Try verifying local files: in the Steam library, right click on the game and select Properties, switch to the Local Files tab and then click on the 'Verify Integrity of Game Cache...' button.
With the GOG version, in the (optional) Galaxy client, 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 that might help identify the cause of the crash?
- 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..."

If you get a VC dll error when trying to start from the executable, manually install the redistributable package.
- Visual C++ Redist 2017, 64bit (Classic uses the 2015 version)
https://go.microsoft.com/fwlink/?LinkId=746572 (direct download)
or https://support.microsoft.com/en-ca/help/2977003/the-latest-supported-visual-c-downloads


Try doing a clean boot and then test the game. For example, there is a known conflict with the Nahimic service used by two audio programs (SonicRadar and Sonic Studio) for certain motherboards which can cause the DE to crash after about a second of black screen, but the Classic release is ok. In that case, there may or may not be an event listed in the Event Viewer for NahimicService.exe, as well as the game executable (probably both 'RADAR_PRE_LEAK_64' events); this should be fixed with the latest updates for the Nahimic drivers and apps.
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.

Try changing the default audio output in Windows. A handful of people have reported crashes in the DE, but not Classic, which could be avoided that way (or in a couple cases fixed by changing, starting the game, exiting and switching back), some related to USB headsets.

Try browsing to the '..\Documents\Larian Studios' folder and delete the 'Divinity Original Sin 2 Definitive Edition' folder.
This folder contains the saved games, configuration files and a level cache folder. Normally I would suggest renaming the folder for troubleshooting purposes, but if you don't have any saved games that isn't an issue.
Next, extract the replacement folder from this download into your '..\Documents\Larian Studios' folder, and see if that will let you start the game.
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 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 any 'CrashDump' files are being created, zip a few together to include.