I’ve done Italy twice, the most recent time this summer. First time was 9 days, second time was 6.
For the 9 days, we started in Rome, without a car. Hit all the obvious spots. Two suggestions here: 1) For the Colosseum, make sure to get the special tours that go under it. Makes or breaks the tour and under it may be one of the coolest things anywhere. 2) For the Vatican, get one of the early morning tours that includes something special and private. There are several variations. We chose to get a private breakfast in the Vatican courtyard catered by Vatican staff from food produced on site. It was amazing. Then a private tour of the Vatican Museum before the public. Other tours give you private access to the Sistine Chapel before the public.
From Rome we took a day trip to Pompeii, using a high speed train to Naples. From there we SHOULD have taken a private car to Pompeii but I was cheap and adventurous so we took a local train which was definitely a way to see the non-tourist view of urban Italy but I don’t recommend it. Pompeii was absolutely amazing, to me. My wife and kids, not so much. It was August and unbearably hot. Keep in mind Pompeii is basically concrete everywhere, radiating stored heat.
After Rome, we rented a car, drove up near Sienna area where I found a private castle for rent. Amazing experience – it dated to about 1,000 AD and we were in the main castle to ourselves (the out buildings were rented to others and the family that owned it were in an adjacent area). That said, a very large bat flew into the living room one night through the massive fireplace so there was that… We used this location as a base for day trips to Sienna and Florence. In Florence, I found a private guide very affordably and they had a special pass allowing us to skip all the lines to get into the main museums, including to see the David, etc.
From there we took the car up to Venice and turned it in then became walkers again. Vienna was special. Flew out of there.
For the second trip, we split between Rome and an Airbnb in a tiny down in central Italy near Lake Bolsena. This was so different and really cool. We had a car and visited small ancient towns all over the region. (It was very easy to drive; the roads even have “Stop” signs in English; and Waze works great there.) The place we stayed was right next to (with a view of) something called “the dying city” (formally: “Civita di Bagnoregio”). It’s impossible to describe but a bucket list thing to see so look it up. This region was incredibly beautiful and so uncrowded (unlike Rome, Pompeii, Florence, Venice).
For the second stay in Rome, we re-did our favorites but also took a day trip to Tivoli (and nearby Emperor Hadrian’s Palace) and highly recommend that. The former has a world famous set of gardens and fountains, the latter is like Pompeii without all the crowds.
Obviously there’s still major regions we have yet to visit (south and north). Good luck.