Florence is the main city setting of Assassin's Creed II's opening sequence.
The game begins in Renaissance Florence, where players meet Ezio Auditore da Firenze and experience his family life before the central conspiracy changes his path. Florence provides the early missions, rooftops, landmarks, and social world through which Ezio learns to operate.
Assassin's Creed II later expands beyond Florence to locations including Monteriggioni, San Gimignano, Forlì, Venice, and the Vatican area of Rome. Its movement between real Italian cities is one reason the title is often remembered as a broad journey through Renaissance Italy rather than a single-city game.
Rome is especially important near the end of Assassin's Creed II and becomes the dominant setting of Brotherhood. Paris is the principal city of Unity, while London is the main setting of Syndicate. The opening city of Assassin's Creed II is specifically Florence.