Well, I played in a MtSC campaign until recently - it ran (troupe-style) for about 5 years. And I must say that I agree that it's a really evocative setting. At first it reminded me of Ars Magica, but as the game advanced the scope and opportunities were greater. At its root, this is a game about the fight for the definition of what is Real. Players can get to be involved in deciding whether there will even be a Renaissance, or whether the mysticism of the past will endure.
Yes, it's a lot of work if you want to set it against an historical background. But keep the scale small, and don't sweat the details, and you can use it right out of the book. Its weakness is perhaps not being clear exactly what the PCs are meant to do, i.e. you need to have a vision of the game to get started. But the play was great fun - and it would probably be fairly easy to port over the new World of Darkness rules mechanics, if that's your thing.