Well, I came back to D&D because I wanted to work within the narrowest, most archetypal fantasy genre. For years, I did very strange, unique worlds that pushed the margins of the genre; one day, I decided it would be an exciting challenge to try to be creative within the genre at its most narrowly-defined. It's kind of like writing a sonnet, or an episode of the A-Team (remember, at 42 minutes past the hour, the team must be building something) -- sometimes it is enjoyable and interesting to produce something when you have all of these confining requirements placed on you. I've found it a bit of a challenge to design plots within the confines of the circumscribed list of spells, nine alignments, carefully described monsters, etc. It brings out a different kind of creativity.
That said, I've done a number of campaigns worlds pretty far off the beaten path. For example, I did a game set in North America in 1247 based on Mormon mythology, Celtic mythology, apocryphal and factural stories of pre-Columbian contact and actual aboriginal histories and oral traditions. One centrepiece scene I never got to do was the Map Room of the Western Northwoods Empire in Saskatoon, where there is a continuous evolving song describing all the locations in the empire, constantly being updated by different people arriving in the capital with their own stories of travel within the empire.
Another game I did was set in a land called Albion, the White Land, based entirely on William Blake's myth and symbol system which was actually set in the far future in a collapsing artificial lunar colony.
Unfortunately, D&D is ill-suited for such worlds; one ends up having to rewrite so many of the rules that you might just as well design a simple set of custom rules instead.
