Shinjuku and Shibuya are good places. Shibuya is a good shopping area for younger 20-somethings I think. Shinjuku is a bit more high end/mature. Try to get a good location more so than a great room.
If you can get a hotel that is close to the Yamanote JR train line, that's probably ideal. Trains are really expensive in Tokyo-as soon as you switch lines the price jumps up. The Yamanote line runs through all the major stops in Tokyo, so staying along that line would mean you wouldn't have to worry about switching trains a lot and will save you a alot of money in train fare.
The first time I was in Tokyo I stayed in Ueno (1/2 an hour from Shinjuku on the Yamanote line) and the fare was under 300yen return. This time I stayed with my friend in Youga, which is really close to Shibuya. By the time I switched trains in Shibuya and went to Shinjuku, it ended up costing me almost double (even though the trip was much shorter).
Ueno has lots of history, but it's FAR. I hated being on the train for so long every day to get to Shinjuku and Shibuya to see my friends.
Harajuku is a good shopping area too. There's some crazy fashion there. La Foret mall has a bit of everything-the basement floors are more goth/lolita wear, but the upper floors have some great fashion that isn't so "out there". There's also a small Topshop/Topman inside.
If you're going with your husband/boyfriend, there's a big Marui Mens department store in Shinjuku. They have lots of fantastic mens boutiques in there. (Oh, and Marui is spelt out like OIOI, so look for that instead of a sign that says "Marui").