I like non-Tolkien/TSR fantasy worlds myself (never was a fan of LOTR or D&D myself), but I think Japan more than has that pretty well covered, and in ways I enjoy. One fantasy world I think would make a great RPG is The Stand, by Stephen King. He did say that The Stand was his version of LOTR set in contemporary America. The Dark Tower universe would make a good game in the right hands.
As far as space goes, I'd like to see more efforts in that area that have no ties to either Star Wars or Star Trek, and not a MMO like EVE Online or Star Citizen (which is looking more and more like it's going to set a record as the most colossal Kickstarter failure in history, anyway), either. Just an open-universe space-exploration RPG along the lines of an EA PC game I played when I was young called Starflight, only with modern technology, with some aliens and combat thrown in.
Real world settings: How about visiting an area of the United States that isn't New York, Los Angeles, or Chicago? What about Texas? Arizona? Tennessee?
I'd also like to see an RPG set in the prehistoric era, with Neanderthals and Cro-Magnons fighting cave lions, mammoths and each other.