For World of Darkness, especially in a MUX, it has to be a city with a population capable of supporting the player population. A global city, a large metropolis of some kind. The Reach in its small-town feel was largely unplayable for that reason. Everyone and their neighbor was a supernatural of some type. Normal mortals seemed to be outnumbered.
Boston could be fun, if it weren't already taken. London could also be fun, if -it- weren't already covered in one of the vampire books, though it has a bit more flexibility at least. Los Angeles is a good city to use for just about anything, as it has universal appeal for both mortals and supernaturals.
Though I do agree with @Pyrephox. Whatever city you make, remember that it has to exist in the setting that you're playing for. If it's a WoD city, then it has to be the WoD version of that city. It has to be... well, dark. Dangerous, slightly sinister and mysterious. It has to have that danger, that draw, that thing that says "come explore my secrets, and hope to get out of it alive".