A different outcome to the Italian Wars could possibly produce a united Italy in the late 15th or 16th century, right around the time the OP managed it in Europe Universalis III. Considering all the political maneuvering and backstabbing of the Italian Wars in OTL, I could certainly see the Milanese, Venetians, Papacy, or some other faction managing to maneuver their way into creating a united Italian state. That also offers the intriguing possibility of creating an Italy which is a monarchy, republic, or even a theocratic state.