I think a sort of endless mod would be cool, like it would be a separate mod from the main game. It could also have a high score and maybe even unlock a new secret character after you've survived a long time that you could play in the main game. I see this happening in 2 ways.
1.
There is an infinitely tall building and you see how high you can make it until you die while every so many floors enemies gain 1hp and also do 1 more dmg. It would be cool if there were some bosses exclusive to this mod, to keep it non-repetitive. I think the xp should be reduced largely, so you can't get overpowered with a million upgrades.
2.
A sort of C.O.D Zombies type of mod where there would be infinite waves of enemies and they would get stronger with each one, and at the end of every wave you would get an upgrade and a small chance of getting one of those boxes that are in the game. Every 10th wave or so there would be a boss and more custom ones would be better so as to not get repetitive. Some exclusive passive abilities could be added to help you in this sort of mod like heal 2hp after every wave or something like that.