The most famous sestiere (district) in Venice has one of the world's most famous squares, St. Mark's (Piazza San Marco). Anchored on one end by the basilica, clustered around it are restaurants, museums, shops, orchestras playing in the square, pigeons, the grand pink Doge’s Palace (Palazzo Ducale), the soaring campanile bell tower, an astrological clock tower, plus gorgeous cafes and restaurants like Florian and Quadri. Piazza San Marco is beloved by Venetians themselves. They book a table anytime, which offers a buffer from the fray. This grand outdoor drawing room attracts Venetians for a stroll too, especially late in the afternoon when the hoards of daytrippers thin out. It's simply a grand place to meet.

Cannaregio is the second largest sestiere (district) with its busy Santa Lucia train station. Many transplanted Venetians commute from the outlying areas, “terra firma” to the locals, which is shorthand for any place that is not Venice. Two Grand Canal bridges serve Cannaregio, the newest (Constitution, 2008) still a local hotbed of controversy. Ponte degli Scalzi is a busy link to the train station. Nearby shops on the Lista di Spagna offer specialties like pastries and coffee that lure Venetians with a down-to-earth attitude. The Ghetto, where the Jewish population was segregated in Cannaregio, has five historic synagogues with an active Jewish community. The Fondamente Nove bustles with foot traffic to the Rialto and San Marco while vaporettos (water taxis) head to Murano and other islands. Side streets lead into quiet picturesque neighborhoods and palaces like Ca' d'Oro rise directly out of the water.

Artsy is the defining mood of this neighborhood with street artists, students, painters, sculptors, restorers, curators, historians, collectors, heirs and heiresses rubbing elbows. Peggy Guggenheim's collection, now a museum, lures chic locals for evening art aperitifs. Traditionalists and visionaries cocoon in bohemian luxury. La Salute basilica buttresses the neighborhood to the east. Gondolas bob in the morning light. The Accademia Bridge crosses the Grand Canal. A back street doubles as basketball court. Palaces house residents, or like Ca' Foscari a university, or a museum like Ca’ Rezzonico that attracts Venetians for concerts. Dorsoduro reveals its industrial roots too, in buildings converted to house university departments or exhibitions. Campo Santa Margherita bursts with youthful energy from local students. Foot traffic bustles to and from Piazzale Roma and Santa Lucia train station. Evening commuters pause for an aperitivo. Neighbors exchange confidants in a campo (square) on their way to market.

The Rialto Bridge is the most famous sight along the Grand Canal in San Polo, smallest of Venice's six sestieri (districts) and by far the busiest neighborhood. Morning Venetians arrive to peruse the markets for fish, fruit and vegetables, while shops display goods from cheese to wine to desserts. San Silvestro and Rialto Market vaporetto (water taxi) stops add to the steady stream of foot traffic. San Polo is defined by churches including Basilica dei Frari, one of the most important churches sought by art lovers.

Giudecca is a retreat for Venetians away from the crowds. Symbolically, six metal teeth represent Venice’s six sestieri (districts); the seventh, Guidecca, points away from the others – part of Dorsoduro, but separated by the Giudecca Canal. Giudecca evolved from a center of shipyards and factories to a quiet residential area with a sprinkling of restaurants and bars. The majestic harmonious Redentore church stands as thanks for delivering Venice from the plague, hosting an annual heartfelt festival.