4 cities to use as a home base?

Do you plan to rent cars or strictly use public transportation?

Most people will tell you that Sicily deserves more than one week, but that's all we had and it was wonderful so I would definitely say it's worthwhile to have one of your bases in Sicily - probably either Palermo for the western part of the island or Catania for the eastern part. But, again, that would depend on if you are willing to rent a car to make it easier to see a variety of places from your base city.

Along with Rome, I would definitely choose Florence for a base in Tuscany - good transportation options to many different towns in the area.

Personally, I might choose Venice for a 4th base but many will tell you that's too much. If it's your first time in Venice it can be risky to commit to a whole week there. For some reason Venice seems to bring out extreme feelings in people - you either really love it or really don't like it - and if you don't like it you're stuck changing plans at the last minute or not enjoying yourself as much as you should. Instead, I might choose somewhere like Bologna because it also has good transportation connections to other places. You could do a day trip to Milan and even to Venice - both less than 1-1/2 hrs by train - plus many other interesting towns (Verona, Padua, Parma, etc.).

Rome
Florence or Siena
Bologna
Venice or Padova
Naples or Salerno

Lots of day trip options

Unless you’re looking for a more small town experience

With all the great regional options in Italy. I would hold off on Sicily until you can give it more time.

It matters a lot whether you're willing to rent a car for part of the trip. Also, what time of year are you planing to go? That would majorly affect where I wanted to stay for a week at a time.

I wouldn't worry about a week in Venice, because it seems most of the people who don't like Venice only stayed there one night, or even daytripped in. That's the worst way to see Venice. However, Padua is also a good posibility in that part of the country. It's interesting itself and it offers a wealth of side trip options. Keep in mind, though, that even staying as close as Padua is not the same as waking up in the magical city of Venice. You'd need to make multiple day trips to Venice, too, and taking that same train trip over and over would get annoying.

I would not be wedded to the one-week-in-each-place time frame. Collect ideas here and read a few guide books to narrow down your top four (or even five) target areas, then think about how many nights to spend at each base.

Sorrento is a great base for the Naples area to see Capri, Pompeii and the Amalfi Coast.

Florence is good to visiting Siena, Pisa and Lucca.

Bologna was OK, but loved Ravenna (not necessarily as a base).

I'll be more specific than acraven on the info that will help us give you the best suggestions and advice.

When? What month? Are you limited to a specific window, like a school teacher would be? My favorite time of year is February/March because the weather's generally mild and it's low season, so room rates are lower and there are fewer tourists at sights. OTOH there's not much scenery to enjoy.

What are your main interests? Art, history, museums? HIking, scenery, adventure? Food and wine?

I could happily spend a week in Venice, it's one of my 2-3 favorite cities in the world. It's the best place to start a trip to Italy because it's the easiest place to relax and simply soak up the atmosphere while you get over jetlag. Walk through some of the back canals, ride the vaporetto (water bus) down the Grand Canal and watch the city glide past. However for a first trip, a whole week in Venice is a lot and it's not the best base for daytripping.

Bologna is a good base, since it's a rail hub. It's mainly a university town; it doesn't have major sights so there are fewer tourists than other places. Opinions are mixed but many, like me, find it to be a charming place. You can day trip to any number of nearby towns, a few of them are: Modena, Ferrara, Padua, and even Ravenna with its stunning 5th-7th c. mosaics. Florence is another with good day trip options and lots to see in the city itself, especially if you want to focus on Renaissance painting, sculpture and architecture.

Naples has a poor reputation but I enjoyed staying there. The National Archaeology Museum is a wow. It's very convenient to visit Pompeii and other towns destroyed by Vesuvius. You can ferry to Ischia and Capri. Or you can base in Sorrento and have easier access to the Amalfi Coast. Salerno is another option.