Are you playing in Windows or OSX?
If you Toggle Multiselect on, select one or more items and then open the Actions menu, does that make a difference?
If you load a save in keyboard and mouse UI, do you have any problem with the right click context menu?
Try lowering the graphics settings and resolution, and switching to Windowed or Fake Fullscreen display mode, to see if that will make a difference.
Are you shutting down all non-essential programs (especially anti-virus) before starting the game?
In Windows:
Do you have this problem if you start the Classic version of the game?
Try exiting out of the Steam client (or Galaxy for the GOG version), 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'.
With the App Store version, or GOG without Galaxy:
Terminal
bash-3.2$ cd ~/Library/Application\ Support\ ... up to the Divinity Original Sin 2.app folder
bash-3.2$ codesign -vvv Divinity\ -\ Original\ Sin\ 2.app
This takes a while, and will output some lines starting with '--prepared' or '--validated'. If everything is fine, it will end with:
Divinity - Original Sin 2.app: valid on disk
Divinity - Original Sin 2.app: satisfies its Designated Requirement
Try doing a clean boot and then test the game.
With Windows, 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.
In OSX, start/restart your Mac and hold the Shift key down as soon as the progress bar comes up in the startup window, releasing it after the desktop appears. Alternately, from the login window, hold the Shift key when you click the Log In button, and release it when you see the Dock.
