Napoli was one of the biggest cities in Europe. Right before the Plague of 1632 hit, it was the biggest, at around half a million inhabitants.
I know. But the biggest does not have to be the most important. It never was the centre of an important empire. Most of the time it was ruled by an non-italian power. Prague and Vienna did not have that size but were centres of history of the timeframe
Also: the decision should stay limited to make it difficult to achieve, more than 5 cities seems to much for me.