Assassin's Creed II begins Ezio Auditore's story in Florence.
Ezio is introduced as a young Florentine nobleman in 1476. The early chapters establish his family, his friendships, and the political world of Renaissance Florence before a conspiracy destroys his household and sends him toward the Assassin life.
Florence remains an important setting throughout the game, alongside locations such as Monteriggioni, San Gimignano, Forlì, Venice, and the Vatican area of Rome. The game uses recognizable Renaissance landmarks, including the Basilica of Santa Croce and Florence's Palazzo della Signoria.
A common mix-up is answering Venice because much of the later adventure takes place there. Venice is crucial to Ezio's development, but Florence is the city where his playable journey starts.