If you want traditional with a twist, I'd go with Sovereign Stone or WoT. If you want a more 2e feel with a twist, I'd say go with Everquest. If you want fantasy in space, go Dragonstar (some rather interesting stuff in there). If you want modern campaigns, you have Spycraft (with Shadowforce Archer) and D20 Modern. If you want SF, you've got Star Wars and Traveller.
If you want a product that is flexible and includes ways of making your own own settings, I'd go with D20 modern, Traveller d20, or core Spycraft (without the Shadowforce Archer setting).
Most of the decision will come from what you want from the product, not necissarily which one is the best. However, I would suggest picking up Spycraft or Traveller, since they seem to have the most meat to them, but if you just want a setting, then any of the ones I've suggested will do you good.