For my money, it's Kalamar. There are SO MANY options out there, you have to be careful what you pick and choose--and Kalamar seems to be a well supported, clear, interesting, and thorough setting.
It's growing expansively--catching up on the sourcebooks and mods for the setting may be an expensive proposition, but then again (like all RPG settings) you simply use what you want and incorporate the new stuff when you want to, IF you want to, at your convenience. All your players really need is to share a Player's Guide and then you can pick up a Campaign Setting Sourcebook. And there's a Living Campaign version to boot.
If you like political intrigue, interesting backstory, and an expansive world with lots of potential for cultural diversification, Kalamar is a good bet. It doesn't rely upon a lot of new races or changed rules to flesh out it's distinctiveness--it's a darker & grittier version of Greyhawk, without the reality-stretching too-high fantasy of Forgotten Realms. Option of psionics, interesting and sufficiently different (but not too different!) new class options, and a wide variety of intriguing equipment. And there's enough that you can start small (in a variety of well defined geographic areas with their own cultural spin) without having to be a globe-trotter to taste what the setting has to offer.
My to cents.
Coreyartus