Are you shutting down all non-essential programs (especially anti-virus) before starting the game? Firewalls have also caused conflicts.
Try starting the game directly from the '..\Divinity - Original Sin\Shipping\EoCApp.exe' program file, by right clicking and running as administrator.
Try browsing to the '..\Documents\Larian Studios' folder and renaming the 'Divinity Original Sin' 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.
After that, see if you can start D:OS and create a new profile. If that works, exit the game and move your saves from the renamed folder to the newly created profile's savegames folder.
If the game still crashes on startup, delete the new My Documents D:OS folder and rename the original back again.
Crash on startup [Solved]