I ran an alternate earth D&D campaing for years, but, partly by coincedence, started using a new fantasy world for 4E. It had is ups and downs. There is a link in the sig somewhere.
One thing I learned is that you can take a lot of different things from "real life". In the last campaign, it turned out that using real life place names (or archaic versions thereof), regions, religious elements, and the ocasional picture or map of an actual place made the campaign more accesible to the players and of course was a great resource for me the DM. Trying to tie in historical events, or details like coinage, period weapons, etc was a little more work, but OK. Though I think I wise not to do more on this front then I did.
Also, I really had to emphasize "alternate" with an alternate history, fantasy locations, archaic names for many places, etc, so the players new that this just wasnt earth 1450, were only their wizard could cast fireballs.