Bangkok is huge, so the right neighbourhood makes the trip. Pick by what you want.
Sukhumvit — best for first-timers
Central, on the BTS Skytrain, with endless hotels, restaurants and nightlife. Easy and convenient; Asok and Thong Lor are popular sub-areas.
Riverside — best for views & romance
Along the Chao Phraya, atmospheric and scenic, with grand hotels and easy river-boat access to temples and ICONSIAM.
Silom / Sathorn — best for nightlife & business
The financial district by day, lively by night, with rooftop bars and good transport.
Old City (Rattanakosin) — best for sightseeing
Next to the Grand Palace and temples; quieter at night, more guesthouses and boutique stays.
Khao San Road — best for backpackers
The classic budget-and-party hub, cheap and social.
Siam — best for shoppers
Between the mega-malls and well connected by BTS.
See also: the full Bangkok travel guide.