Eberron for me! It has many elements I really, really like but the setting just doesn't jive for some reason.
I think it has something to do with the "fragile" peace of the 5 nations. Nothing really *big* can happen as far as conflicts go in Khorvaire, not without setting everyone off and engulfing the continent back into war. Everyone is war-weary one way or another and seem just interested in moving on with their lives peacfully. That and no deities being active, they're pretty much ignored and used at convenience, and alignments are for the most part ignored as well. Why not just do away with alignments entirely in an original move for the game setting (borrow Allegiances from d20 Modern at least)? Action points fall flat as well in their execution abit, their nice to have but nothing too exciting without taking a prestige class and feats.
A minor nitpick is there are so few books out so far that support the setting (no magic book or monster book yet) that I find little to build characters with. Couldn't they have released some kind of player's guide at least?
I really, really want to love the setting, with their shifters, warforged, flying ships, Sharn, wonderfully written background info, etc. it's just poorly executed as far as game mechanics go. Nothing at all orignal or provides a substantially unique flavor/tone to the setting.