I've been spending most of my reading time these days with George R.R. Martin's "Song of Ice and Fire" series. I was introduced to the setting through the excellent HBO adaptation, but quickly decided to read the books as I was sure that there was deeper content, and more of it. I was not disappointed.
Of course, we all know that the series has been adapted as a roleplaying game (though to be sure, I don't know very much about the game and how well it adapts the material; it seems to me that HârnMaster would go a long way toward developing the feel of the setting, with some work adapting the terrible and exotic magics of Martin's fantasy). There are a few other literary settings that have been adapted by specific roleplaying games: Tolkien's Middle-Earth, Vance's Dying Earth, Moorcock's Melnibone and some other Eternal Champion material, Lovecraft's Cthulhu stories, Niven's Known Space, Fleming's James Bond (though perhaps that was more an adaptation of the movies), Constantine's Wraeththu, Herbert's Dune (twice, though only once officially), Butcher's Dresden Files, Zelazny's Amber, along with a very few others. This doesn't include those settings that were mere supplements for other games, such as Thieves' World, Wild Cards, or Adams's Horseclans. There are even a few, such as Howard's Conan, that have been adapted more than once. In addition to those, there are some movie and television settings that have seen adaptations, like Star Wars (three times so far!), Star Trek (more than three times, depending on how you count it!), Firefly, Babylon 5, and so on.
However, there are some settings of fiction that have not been adapted to roleplaying games, and I am not sure why that is. Eddings's Belgariad, Erikson's Malazan Book of the Fallen, Butcher's Codex Alera, Burroughs's Barsoom (well, it sort of has, but not really), Lee's Flat Earth or Birthgrave, Donaldson's Thomas Covenant, Brooks's Shannara, and so on. Some of them, I can understand if the rights have issues or are otherwise difficult to secure, but the popularity of such as Malazan or Shannara would seem to have caused someone to go through the effort.
What settings do you most want to see turned into freestanding roleplaying games? Which would be better off as a supplement for an existing game like D&D/Pathfinder, GURPS, BRP, or whatever?