If we're talking the Italian maritime republics, I don't actually see Venice as being in a great position. It's power/wealth and therefore it's ability to defend itself is based on it's trade. There's plenty of ways to cut off their ability to trade with the Near East, and considering that any PoD would probably be after the rise of the Ottomans and Enrique the Navigator, then the Portuguese will undercut Venice's trade with the East, the foundations of their wealth. Sure, Venice is in a good defensive position, but that won't last forever. Older fortresses will degrade and will be unable to counter emerging weapons technologies, and Venice won't have the money to upgrade them. Additionally, Venice is too-close-for-comfort to Austria, which was a major player in Northern Italy, and with their acquisition of Dalmatia, they can economically strangle Venice as the Venetians eventually grow unable to afford a powerful fleet. To be honest, it's amazing that Venice managed to tread water as long as it did.
Genoa too is in a similar position, it's Black Sea trade being cut off by the Ottomans, Tartars and later the Russians, while it's possessions in Greece are threatened by the Ottomans. The least vulnerable Italian city-states are in Central Italy, North of Latium and South of Lombardy, such as Pisa and Lucca. Pisa was snuffed out too early, but a Lucca that expanded and took Pisa would in effect be a maritime state. It isn't hard to butterfly away Napoleon, and therefore the events that led to the unification of Italy.