Once Upon A Time in the West
I know we've had "elves and dwarves in the Old West" and "let's have a lot of fantastic things going on in an alternate history Old West", but I'd like to see something more like the post-Apocalyptic, sort of Arthurian, fantasy Old West of Stephen King's Dark Tower series. I'd settle for the more-coherent-than-Deadlands alt-history fantasy of Mark Sumner's The Devil's Tower, or Orson Scott Card's Alvin Maker series, which is even better, but really pre-classical Western era.
Hairy primitives and their dinosaur companions (or vice versa) versus more belligerent hairy primitives, prehistoric monsters, and space aliens. In other word's Jack Kirby's Devil Dinosaur series exploding into rpg form. It would be a lost world well worth finding.
Giants in the Earth
Take parts of Exalted, but emphasize the Biblical inspirations, and combine it with some wild-eyed von Daniken-esque fantasizing, preferably in the key of Kirby's (him again!) Eternals and put it all in a Sword & Sorcery prehistory. Nephilim tread the jeweled thrones of the earth under their sandaled feet.
A Different (Head-)Space
I'd like an action/adventure space opera with a little bit more of the trippiness of Dune, particularly as it would have been adapted in Heavy Metal or Epic magazine. Star Wars informed less by Alex Raymond derring-do, than by Jim Starlin psychedelia. Something more like Dreadstar, Metamorphosis Odyssey, or European imports like The Incal, or Metabarons.