When is the crash occurring?
Are you shutting down all non-essential programs (especially anti-virus) before starting the game? With the original release of the game, a few people had McAfee's real time anti-virus scan cause startup crashes/errors related to SDL2.dll (and osiris_x64.dll); and adding the files to the exclusion list would fix that.
Can you start the Classic version of the game?
Try exiting out of the Steam client, of applicable, 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).
If applicable, disable Steam cloud support either globally (in the client click on the Steam menu and select Settings, and then Cloud) or just for this game (in the library right click Divinity: Original Sin 2 and select Properties, then switch to the Updates tab and check the Steam Cloud section).
Alternately, exit out of the Steam client, or Galaxy for GOG, and just start the game directly from the executable when required.
Next, try browsing 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. With Steam / Galaxy running and cloud support enabled, the client would just download the cloud copy of your existing profile.
After that, 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. It also contains an option set which can help if the problem is related to hardware acceleration for cloth physics (for an issue that can cause a startup crash with the DE, but does not affect Classic).
If that helps, create a new profile and continue, or if you have saves from an existing playthrough, exit and copy the profile folder from the renamed folder into the newly created PlayerProfile folder.
If the game still crashes, delete the replacement My Documents D:OS 2 DE folder and rename the original back again.
Try creating a new Windows administrator user account, do a clean boot (see below), log into the new account, and then test the game by starting it directly from the executable. Actually, you could try just a new account first, without the clean boot, and see if that helps.
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.
