Greyhawk got my vote for fantasy. I liked it when it became the default setting for 3e since I was familiar with many of the concepts and names but not much setting detail. It was fun to learn more about it, especially from a 2e supplement that a player loaned me that I subsequently bought used.
Spellslinger is the runner-up. This is a great mini-game for western-themed D&D. Sadly, the player that I thought would be most interested in playing it is moving away; so it is effectively dead. Too bad. I found it much better than Deadlands (which has a great game mechanic), Deadlands d20 or Sidewinder (which has a neat presentation).
Skull & Bones gets an honorable mention. The new & variant d20 rules don't add anything to my low magic pirate D&D camapign, but the setting information is outstanding.
Forgotten Realms deserves an honorable mention. The default could just as well have been Forgotten Realms for me, and I would have enjoyed that too from having read so many FR novels.
Conan deserves an honorable mention, too. Not the OGL d20 Conan published by Mongoose--it presents too many unnecesary changes for my taste. I'm talking about the Conan RPG from TSR circa 1985. The third module, CN3 Conan Triumphant, is a great story; and that's why I would give the setting an honorable mention. It was so good that I bought the book, and it is not a Howard story.
Gamma World/Omega World would get my #1 non-fantasy vote right now. I just finished running a mini-camapign using the Alternity GW story line with the OW d20 rules. Although my Rifts to DragonStar to Omega World conversion campaign died an ignoble death due to player boycott, another DM has an old Rifts campaign using the Gamma World Legion of Gold module converted to Omega World that I love. I wish we played it more. Incidentally, Rifts and DragonStar are great concepts but suffer from a lack of DM usability and adventure support.
Judge Dredd d20 is the non-fantasy runner-up. I really like the whole concept, especially the adventures. I haven't been able to sell my group on it past the first 2 adventures (and only a few members at that), but I really like the setting. I even got some comics and computer games after reading the game books.
Star Wars, of course, gets an honorable mention, too. I just haven't been able to play it enough since the DM is a little flighty. Also, my comrades have a tendency to turn it into D&D in space.