The Middle, that’s it. The heart of Berlin is where most of the sights are, so booking a hotel in the area is a good choice. Mitte, however, is rather vast and there are quite a variety of zones within it. From the super touristy Friedrichstrasse, where you find Checkpoint Charlie, the Brandenburger Gate and fashionable stores, to trendy Auguststrasse and Torstrasse, at the Prenzlauer Berg border, to the always busy Hackescher Markt and, last but not least, to Soviet-style Alexanderplatz. The rule is, the further East you go, the better it gets.
My favorite areas: Alte and Neue Schönhauser Strasse, Auguststrasse + Tucholskystrasse, Torstrasse + Rosenthalerstrasse, Montbijoupark + Museum Island.