You are saying 320 x 240 is killing monitors? :)
If the monitor doesn't support it (likely on an old monitor), and it doesn't have 'out of range' checking (much more likely on an old monitor), and the drivers windows are using are not adequate (incredibly likely on a standard 'plug and play monitor' driver), it will bust.
The default flag for the GRAPHICS command is "0" witch means windowed in debug mode and full screen in non-debug
The two modes shouldn't be so much different that it makes things completely different for each mode. But there are some things about windowed mode, mostly Windows limitations (ie the desktop is not double bufferred), that you may have to watch out for maybe.
Some games _need_ to be in 320 x 240 for the classic 486/
Again, if you want that so bad, use 640x480 and doublesize the graphics.