Shinjuku and Shibuya offer the best transport connections (multiple train lines intersect) and suit first-time visitors. Asakusa has the most traditional atmosphere near Senso-ji. Ginza is upscale and central. For budget stays, capsule hotels in Shinjuku are a uniquely Japanese experience worth trying once.
Akihabara suits tech and anime fans; Shimokitazawa attracts the indie crowd. Business hotel chains (Toyoko Inn, Dormy Inn) offer clean, reliable rooms with onsen for $60-90/night. Luxury hotels — Park Hyatt (Lost in Translation), Aman Tokyo, The Peninsula — are world-class if budget allows.