Six sestieri on the main island, three inhabited islands, one mainland alternative. Pick a neighbourhood before you pick a hotel: the walking time to the nearest vaporetto stop matters more than star rating for a three-night trip.
Six sestieri, quick take
San Marco: first-timers, palazzo stays, five minutes to the Basilica. 18 min from Santa Lucia on foot.
Cannaregio: slower Venice, cicchetti evenings on Fondamenta della Misericordia, quiet before 10am. 10 min from Santa Lucia.
Dorsoduro: art-first, Zattere at sunset, quiet residential mornings. 20 min from Santa Lucia.
Santa Croce: arrival sestiere, easy on luggage, family-friendly. 5 min from Santa Lucia.
San Polo: bacari and Rialto market, San Giacomo at dawn. 15 min from Santa Lucia.
Castello: Biennale sestiere, residential calm, quieter than San Marco at any hour. 25 min from Santa Lucia.
The mental model
Venice is a walkable city, and the hotel decision is a sestiere decision first. A hotel that ignores the vaporetto stops around it is a hotel that will make you drag a suitcase over four bridges. Once you know which sestiere fits the trip, the hotel shortlist narrows quickly.
For a first visit of two or three nights, San Marco or Santa Croce shorten the walking day. For a returning visit, Cannaregio and Castello reward the effort. Compare side by side at where-to-stay/compare.