For years I was stuck with a setup where my main monitor was plugged into the GPU via HDMI, but my secondary monitor only had VGA, for which the card did not have a port. My motherboard does have one, though. Using that basically worked... with random issues popping up both now on Linux and way back in the dark times.

One of these issues was that FO4 would not display correctly in full screen. It looked fine in windowed, but the cursor would be confined to the top left area of the screen, unless I had my second monitor, physically on the left, virtually on the right instead.

I just inherited a new card and I took the financial hit of a cheeseburger's worth for a VGA-DisplayPort adapter, and now it works just fine in full screen!