I use Greyhawk as the main world and placed Iron Kingdoms in an area above the Scarlet Brotherhood lands.
I've scanned through a fairly rough version of Iron Kingdoms, but I certainly never thought of plopping sections of it into GH. Still, the Greyhawk setting, as great as it is, is a standard bit of fare today. It remains as a marker with which to weigh out other fantasy settings, many of which fall quite short of GH's acheivements.
For Fantasy, I would list Talislanta as a very different fantasy world.
If the book's setting holds up as well as its artwork does, then this is truly a damn fine setting. Alas, I've been trying since the 80's to get a copy, failing to do so for various reasons. One day I'll get off my duff and order the version in stock.
Barsoom
Knock yourself out.
It most certainly did, especially after learning that Burroughs' Carter series was the inspiration for Dark Sun, though it took someone pointing that out to me before I made the connections. BTW, great job in converting the novels into a worthy game structure (I've had your site bookmarked for some time now

). But still, in all fairness, what do you feel is particularly original about Burroughs' setting (I'd rather let you answer that than fill in my own as I'm fairly sure that your the more knowledgeable one here).
The Old World [snip] no other campaign setting is so... so... grotty.
Grotty? Is grotty really a word? Even if it isn't, it certainly applies. Never thought I would hear someone using a toilet analogy for an RPG
in a good way, but it fits the dirty, ruined feel of the Warhammer setting.
Anyhow, here's another from me (I think my brain is just on a sci-fi kick lately):
Blue Planet
While water worlds have existed in fiction for some time (Clark's The Songs of Distant Earth comming to mind, although even that was only the mid 80's), I'm fairly sure that this is the first RPG to dive under the waves. The science presented in the book is quite sound, without being overwhelming to those who don't have a college degree in oceanography. The interactions with now sentient whales, dolphins, and other marine life is done with taste, and not comical by any means. The history and current politics are very tightly woven and require very little suspension of desibelief. All in all, a damn wet game that is, I think, original in its presentation.
Here's another, less serious one:
Paranoia.
I hate comical RPGs. I love Paranoia. I hate taking time away from role-playing out another overly melodramatic character in a grim, dark, and serious game. I love playing Paranoia. I thought of comical RPGs as silly and childish, but Paranoia's unique quarks made me laugh till I ached all over the first time I played it, and still does. Originality (and absurdity) are mainstays of the setting, even when it borrows heavily from films, novels, and even other RPGs. The whole idea of clones itself is a riot; wondering how your current character is going to get blown to smithereens by his (your) own incompetence, yet not caring one bit. Any other humorous RPGs out there stand on a single hook, or basic premise, which of course makes the laughter grow very stale very quick. I still try and sqeeze in an all night Paranoia game (preferably late at night, when delirium and sleep deprevation start to kick in).
(edited because quotes never appear where I put them!! Grrrrr!)