Are you shutting down all non-essential programs (especially anti-virus) before starting the game? Firewalls have been known to cause this problem; overlays from graphics tweaking/monitoring programs or chat programs can also caused issues.

Try exiting out of Galaxy, and starting the game directly from the '..\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 right clicking the executable, select Properties, switch to the Compatibility tab and check off the 'Override high DPI scaling behavior' option (set it to Application), maybe run as administrator and disable fullscreen optimization, and set a Win 7 or 8 compatibility mode.


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.


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.