Where to have home base?

Will you be renting a car, or using trains and buses? If using public transportation, Florence will be ideal for nearly all the places you mention... Although some places are certainly worth more time than a day trip would allow. With a car, base yourself in an agriturismo somewhere in Tuscany, like just outside Siena or Lucca.

BTW... There are too many "do not miss" places in Italy to cover them all in a 2 week long trip. Pick 3-5 locations that really matter to you, and save the rest for next time.

Yes, don't mind renting a car at all. We realize we will want to come back once we go there the first time! If you could choose 3-4 places to go, what would they be?

"If you could choose 3-4 places to go, what would they be?"
I'd say Venice, Rome, Florence and the Amalfi Coast. But it depends on what you want to see -- natural beauty or churches, art galleries, and museums.

Well, that is a tough question! My first trip I went with a friend, so there was a lot of compromise involved. We went to Stresa (lake Maggiore), Verona, Venice, Florence, Siena, and Rome. Of all those places I liked Rome the least, but it may have been because I was tired and cranky by then! I should have chosen fewer places and stayed longer. The places I liked best were Stresa, Verona and Siena.

The trip I am planning for this October/November will be just ME and is a bit longer, so I can go where I like and linger a bit. I'm flying into Rome but only staying one night before heading to Sorrento and the Amalfi coast. Then I'll be spending quite a bit of time in Umbria, staying in Orvieto and Assisi. Then I am going to Florence to check out some of the things I missed on my first trip, and spending the last 2 nights in Milan before I fly home.

I'm also keeping in mind some places for the next trip! Hubby dear wants to go to Cinque Terre, Tuscany, lake Como, Venice, and Rome. It'll be nice to discover some of those together.

Are you planning to do all of this from one location? It sounds as if you might not understand how big Italy is. Check out this site: Compare Italy to US state

For two weeks, you'd be better off moving from place to place, staying at least 3 nights at each location. The trains in Italy make this easy and economical to do. There's no reason to rent a car on your first trip to Italy, imho.

Fly into the north and work your way south, flying out of Rome or Naples. Or the reverse, flying out of Milan or Venice.

Two weeks is really 12 days on the ground, since you'll lose a day on the flight over, and day of departure doesn't count. I'd choose three cities and day-trip if you like from those locations. Most people do Rome, Venice, Florence. You, however, may choose Florence, Rome, Amalfi Coast of Cinque Terre. This gives you 4 days per city, or dividing them differently.

IMHO Rome and Florence deserve more time. From Florence you can see a good bit of Tuscany, if you choose to spend 4 nights there, one day-trip to Siena, and one day to book a wine tour which will give you a full day of roaming the Tuscan Countryside while affording a chance to drink some wine. Florence itself deserves a minimum of two full days! Rome deserves four, and you can do a few day trips from Rome as well, including Ostia Antica or Ovieto. Venice can be done in two days.

If it were my first trip, I'd fly into Venice, spend 3 nights (because of jet lag, and Venice is a calm city), train to Florence, spend 4
nights, train to Rome and spend the remainder of the time there and do a few day trips. I'd eliminate Cinque Terre because it's not the ideal time to visit that region anyway. That's my advice.

Awesome advice for an Italy newbie. I will move around and spend 3-4 days per city. Thanks all!