Good idea, I think this is one area where Quake has remained mostly untouched. Anyways, here's my suggestions:
* Replace DMFlags with a generic option, should fit with the context of the game mode.
* Replace the functionality of shortcuts and batch files with a flexible frontend.
* Remove outdated/redundant options from the menu.
* Allow people to join a server from the web browser.
* Modernize the HUD/UI, keep them simple and make it a mouse-driven interface.
* Replace 'new game' during multiplayer with a multiplayer-specific screen that allows you to choose levels, max players, friendly fire, admin controls, etc... allow people to see the levels on the menu too.
* Better editing tools that alleviate restrictions rather than providing work-around solutions.
* Standard FPS controls by default, each mod should have it's own custom list.
Attack - Mouse 1
Previous Weapon - Wheel Up
Next Weapon - Wheel Down
Move Forward - W
Move Backwards - S
Step Left - A
Step Right - D
Run - Shift
Jump - Space
Crouch - CTRL
Inventory - I
Use Item - Enter
Previous Item - [
Next Item - ]
Drop Item - Backspace
Talk - T
Team Talk - Y
Scoreboard - TAB