Florence FLR or Pisa PSA (50 miles from Florence) only have inter European flights. So from CLE you would likely need two layovers.
The only exception may be AirLingus, which flies directly from CLE to DUB in Ireland. AirLingus flies directly to PSA from DUB, but only in summer and I don’t think they have mor than a few flights weekly, so that option may or may not work for you.
Returning from Naples NAP, ha similar challenges. Naples has mostly European flights, except United which has non stop seasonal flights to Newark (EWR) and Delta, which has non stop seasonal flights to JFK, and ATL. Those seasonal options are available only in summer.
But if you chose Air Lingus going (to PSA), via DUB, then returning from NAP via Air Lingus would also be possible since Air Lingus also flies from NAP to DUB (in summer only, since it’s a seasonal flight).
So, to make a long story short, if you want to fly to Tuscany and return from Naples NAP, and minimize the number of layovers, then Air Lingus via DUB is the best option.
If you want to fly to Rome FCO and return from Naples NAP or return also from Rome FCO, then you have multiple options with one layover only (with Delta via JFK or ATL or with United via EWR). Obviously to return from Naples you need to fly in summer. To and from Rome, there are plenty of options all year around.
Flying to Rome (and from Rome) is not so bad, since Rome is well connected via high speed train to both Florence (90 min) and to Naples (70 min).
If you select a flight to return to/from Rome FCO make sure you leave your Rome days for last. So, if you arrive at Rome, go immediately by train to the next destination (Tuscany or Naples), then move from that destination to the next by passing Rome. The high speed train from Florence to Naples, for example, takes only 3 hours, downtown to downtown.
Leave Rome for the last few days of your visit before flying home. Always stay in the city where you return from, as the last place you visit in your itinerary.