I should think this would be more a General discussion thread than a House Rules thread, at least in the beginning...... Also, more people read the General forum, so replies are more likely.
In any case, my brief response....
1) Most importantly, I would think, is that it has to be different enough from the main, pre-existing settings, to be distinguishable and not dismissed as 'just another Middle-Earth/Faerun clone.'
2) Yet it probably needs to be similar enough for folks to be comfortable using it, without challenging too much of their familiarity with standard D&D.
3) It needs to feel reasonably consistent and not a hodge-podge; some main themes and guidelines.
4) It probably needs to allow for, and at least occasionally include, many of the supplements and variant rules and such that people have come to prefer/expect (and spent money on) from 3.x. Like allowing for incarnum to be used, allowing for psionics, and stuff like warlocks and binders and whatnot. Some elements might be integrated with it, while other stuff should just allow the possibility (like no hard and fast rule against a particular type of magic possibly existing somewhere in the setting, and some mysterious/distant lands where such might exist). Or whatever.
5) And of course, it has to include in some way, shape, or form, ninjas, dinosaurs, and pirates.

And have some sort of interesting and unique/strange areas, organizations, creatures, or whatnot.
I have nothing more constructive to say for now.