Midtown Manhattan — maximum convenience
Close to Times Square, Broadway theaters, and several subway lines that reach everywhere else. The trade-off: it's the most tourist-priced part of the city, and can feel impersonal in the evenings once the offices empty out. Good for short trips built around sightseeing and shows.
Upper West / Upper East Side — quieter, still central
Residential, closer to Central Park, and noticeably calmer than Midtown at night, while still a short subway ride from everything. A better fit if you want to feel like you're staying in an actual neighborhood rather than a tourist zone.
Lower Manhattan / Financial District — value plus views
Hotel prices here can undercut Midtown, especially on weekends when the financial district empties out, and you're close to the Statue of Liberty ferries, Brooklyn Bridge, and the 9/11 Memorial. Fewer restaurant options in the immediate area once you're outside business hours.
Williamsburg, Brooklyn — for the food and the view
One subway stop from Manhattan (the L train) with some of the city's best restaurants and bars, plus a waterfront view of the Manhattan skyline that most people staying in Manhattan never get. Slightly less convenient if your itinerary is Manhattan-landmark-heavy — budget the extra transit time.