I think Shinjuku is a great home base. I've enjoyed several stays at Keio Plaza, but prefer the nearby and somewhat smaller Hyatt Regency Tokyo (formerly Century Hyatt). The gym is nice, and on a clear day I was able to see Fuji-san while working out. I've also tried staying in the Ginza / Imperial Palace area (Imperial hotel). While a nice hotel, I liked being in Shinjuku more.