Crash on startup, used to work

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.

If you have any generic or obscure USB controllers (or other devices) plugged in, that you were not using when the game was working, try disconnecting them. Crashes on startup with faulting module names of ntdll.dll and EZFRD64.DLL, can (particularly for the latter) be related to USB controllers or PS2 to USB adapters (for various games).

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 Files...' button.
With the GOG version, in the (optional) Galaxy client, select the game, then the settings icon at the top right (beside the Play button) and under Manage Installation select 'Verify / Repair'.

Especially if the game gives a VC related dll error when starting from the executable, try installing the 2017 Visual C++ redistributable (64bit), now included with the 2019 release. In the Control Panel, Programs and Features, try right clicking the MS VC++ 2015-2019 redistributable entries (32 bit and 64) and select Uninstall and then Repair.
C:\Program Files (x86)\Steam\SteamApps\common\Steamworks Shared\_CommonRedist\
C:\Program Files (x86)\GalaxyClient\Dependencies\__redist
or https://support.microsoft.com/en-ca/help/2977003/the-latest-supported-visual-c-downloads

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 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 the GOG version, 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, see if you can start D:OS 2 DE. If so, create a new profile and maybe check that you can start a new game and save/load. If that works, 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 crashes, delete the new 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.

Try creating a new Windows administrator user account, switch to that account and try starting the game from there, directly from the executable.

If that doesn't help, please contact support 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.