[modeless]

You certainly could. You would probably run into a lot of issues in areas that games don't care about that much like multiple windows, smooth window resizing, fancy text layout and input, fast initial load times, matching OS themes and widget behavior, low resource usage at idle, copy/paste/drag/drop, software rendering, etc.

[ClawsOnPaws]

Add accessibility to that list. Screen readers, magnifiers, switch controls, etc. Usually game engines don't support these while your native OS UI probably does, and the web is also not bad in that regard.

[jamesgeck0]

IIRC there is actually an ongoing Godot accessibility effort.