For single player, Florence can have permaclaims on all its neighbors on 12 november, through the missions; you can attack neighbors by 12(?) december. What I did is restart until you can snipe 1-2 not allied yet OPM's; not setting any of them as rivals makes them less likely to get allies. Once you conquer the OPM to your south, you can manufacture a claim on Naples; If you declare on them the moment they're independent it's usually free land.

After some of this, you're usually big enough to ally Austria and/or France; this is where the fun begins. Navigating alliance networks is tricky, but fighting your rivals if they're not cobelligerents is great. You can get them to release nations, break alliances, take their money etc. and then destroy them in the next war. Releasing OPM's and then diplo vassalising them is also a good way to expand once you get big enough, since it gives no AE. The money you get from bullying them can also go to mercenaries, allowing you to easily punch above your weight.

Sometimes, attacking someone who is an ally of the French (for example) while you're also an ally of the French, makes them stay neutral & you get free land. You can pit allies against each other by declaring on someone else & ensuring two allies end up on different sides of the war. You can call in someone, and then snipe an ally of theirs since they can't declare war on you. Doing all of this lets you easily grow to be the strongest state in Italy.

You have to embrace the Machiavellian way of playing the game. Machiavelli was born in Florence, after all.