The biggest problem with Berlin is that it is very spread out and there is no single tourist zone. The good news is Berlin has excellent public transportation and is very human scale (not a huge confusing urban jungle) and very walkable.
Theres a ton to see in the former west and a hotel near the Zoobahnhof (or Rick's much loved Savinyplatz) would be good. Then theres a ton to see in the former east with Alexanderplatz as the center. Then of course theres Berlin Mitte, considered the central core of the city with the Brandenburg gate, the Riechstag and the new grand Hauptbahnhof.
You will need a combination of Ubahn, Sbahn and walking no matter where you stay. My recommendation would be for a hotel near Alexanderplatz or Hackischermarkt station. Great selection of restaurants, you have buses, streetcars, subway, and commuter rail all nearby.
My few trips to Berlin were mostly business so while I can highly recommend the Radisson Blu in Mitte or the Park Inn at Alexanderplatz, Im not sure these would be the right hotels for you. Im sure others on this board will have better suggestions. But this should give you a better idea.