The first idea I had is to paste together everything I like in fantasy, so to create a world in which I have a spot for every weird idea pops into my head and use for future attempts. Things to throw in include: a pirate archipelago, a sky realm, Transylvania, a dark desolation of chaos, primitive lands for swords & sorcery, a couple of different human kingdoms (vikings, medieval knights, despotic technocracy) and a lot of empty space for future addenda (desert land for Arabic themed adventures, an uncivilized land, a Japanese themed country, and so on). So yes, basically nothing too different from Mystara. Creating a brand new world has its benefits on the long run (that is, re-usability), but its nonetheless one hell of a work even if one limits his efforts in barely sketch up everything focusing only on what's really needed.
Middle Earth Hack
I'm toying with this idea since, like, always. I think hacking the Middle Earth could really provide me with a very interesting world for a D&D campaign. Of course, the hack part is where I put in everything D&D-ish (like common high-magic, clerics, powerful magic-items and artifacts, Dwarf Rangers, Gelatinous Cubes, etc.) with little attention not to denaturalize Tolkien's masterpiece. The benefits on the short run is that I would only need to adjust what is worth (like, for example, place the Witch-king of Angmar among with Sauron and Smaug all in the same time-line) and already have a general idea of what's where, and how the world scale works (I always have hard times with this kind of things). The major drawback I see here is the limited re-usability of such a setting.
A Possible Solution
How about using the Middle Earth hack as a base for the Fantasy Mashup world? Like, it's obviously the western portion of a larger continent, and many of the things I wish to include (oriental, Arabic, Viking, medieval kingdoms, etc.) are already in one way or another. I could make it work by reorganizing it's geography (for example, switching Rhovanion and Eriador, Mordor and Angmar, making room for Transylvania in the eastern part), changing most of the names (except the generic ones, like I don't know, The Misty Mountains) and so on.