I'm not a downtown kind of guy. I'd rather have a farmhouse than a flat/apartment (or even house) in the heart of a city.
If I were to live in a downtown area, Id have to go with Tokyo, I think. Great mass transit. Very clean. Very safe. Maybe London after that?
In the US? I don't know. What's the best downtown area in a US city? I'm talking major cities. Cities like Burlington, VT don't count.