In Assassin's Creed II, the San Marco district is located in Venice.
Ezio reaches Venice during the later part of the game, where he investigates conspiracies and works with allies including Leonardo da Vinci. San Marco is one of Venice's recognizable districts, represented through landmarks and canals that support climbing, travel, and missions.
Florence is another major city in Assassin's Creed II and is the setting for much of Ezio's early life. Rome becomes especially important in Assassin's Creed: Brotherhood, while Forlì appears as a separate location in the second game. These nearby Italian settings are frequent sources of mix-ups.
The real San Marco area is associated with St Mark's Basilica, the Doge's Palace, and St Mark's Square. The game adapts the historical city rather than reproducing every building exactly, combining documented locations with fictionalized events.