Do reprints count? Because I'd love a Marvel Essentials-style series of TMNT reprints.
Sam And Max Plunge Through Space would be awesome as a graphic novel. Steve Purcell's said that he's considering it.
And a Duke Nukem comic would be awesome. It'd actually be a good fit for Rob Liefeld.
The closest thing that we can get to a Howard/Donald duck crossover is this
.
That said, I rather like the idea of an epic crossover between all the big comic universes. Including CLAMP.
Ukrainian Red CrossHellboy has to go to Hell for...SOME REASON and finds himself bombarded with Hell Spawn!
They're too similar. Good for a short story though. In fact I think they have met, it'd be weird for two of Dark Horse's biggest (creator owned) comics not to meet.
A comic book series based on the Megaman cartoon. I think there WAS supposed to be one, but it got canceled.
The Protomen enhanced my life.

No, they discovered a time pod
which the effects department made to resemble a TARDIS.
Ukrainian Red Cross