Florence is the Assassin's Creed II city associated with Medici rule.
Ezio Auditore's story begins in Florence, a major center of Renaissance politics, banking, art, and scholarship. The game portrays the city during the period when the Medici family held enormous political and economic influence, especially under Lorenzo de' Medici.
Florence is one of several Italian locations in Assassin's Creed II. Players also visit Venice, Forlì, Tuscany, and Rome, while Monteriggioni serves as the Auditore family's base. Leonardo da Vinci helps Ezio with equipment and interpretation of ancient discoveries.
Venice is the most common mix-up because it receives a large portion of the game's later action. Rome is another plausible answer because it is central to Assassin's Creed Brotherhood, but Florence is the city where Ezio's personal story and initiation begin.