Get a hotel downtown. The Hilton and Holiday Inn are good choices. You can even walk downtown and there is the "Deutsches Museum" right next to it. http://en.wikipedia.org/wiki/Deutsches_Museum

There are also some nice Hotels around the Mainstation (Le Meridien, Sofitel etc.), but probably more expensive than the Hilton/Holiday Inn.
Enjoy your stay - there is lots to see downtown and a lot of restaurants and good beer ;-)