D&D campaign idea:

Have players make modern-day human characters, but they must be a caster class. Their characters are ordinary people who have been augmented by transdimensional alien powers (change fluff accordingly).

All classes now also have a 0-level spell called "Dimensional Mending". This is a full-round action that can only be performed on a dead alien, sending the corpse back to its home dimension.

PCs have been recruited (press-ganged?) into a global military force that defends Earth from alien incursion, and they've given strange alien powers to the PCs to achieve that. They are now S.T.I.N.G. : Specialized Transdimensional Incursion Neutralization Group.

At random times, D&D monsters (with fluff changed around to make them suitably alien) appear on Earth, and the team is scrambled to go take them down ASAP.

The hurry is not because the monsters can't be taken out by civilians - it's because, dead or not, the monster acts as a tear in reality that allows a new monster to come through every few minutes.

The PCs are the only thing standing between humanity and apocalypse. They get airdropped into random environments, and have a limited number of rounds to find, kill, and cast Dimensional Mending on whatever magical beast is there.

(As they level up, magical items (with alien fluff) become available. The PCs don't have to spend their own money, of course, but they choose what gets "augmented" from a limited pool based on GP value.)

There is a high-level cleric back at base that can rez dead PCs, so even if you TPK, you just wake up and the brass tells you that another team had to come in and clean up YOUR mess and retrieve your bodies. (Which means that sometimes your mission is to do the same for them.)