shelbo has good advice with driving some parts and not others. One thing people tend to forget is that most countries in Europe are much smaller than places in the US. You can drive from Sicily to Naples in about 6 or 7 hours. That barely will get you across Virginia here. So it is feasible to have a car for a day or two and hit a lot of countryside locations.
But that brings up another point. Sure there are some quite little villages and towns in Tuscany. And the rolling hills are beautiful. But you can get that here. There are a lot of little quaint places in the US that you can visit if you want that “small town relaxed” feel. Up and down the Blue Ridge mountains I can think of a dozen spots to go that would give you the same feel…up to and including some small vinyards for wine tasting/tours. So I personally go to places like Italy for what I can’t get here. Namly architecture and ancient stuff. Colonial Williamsburg just doesn’t quite stack up to Rome…know what I mean? Of course this is just MHO and YMMV.
With what you mentioned as your interests, I’ll recommend some cities and sites within the cities to visit. This is obviously just going to be the highlights. There are more things to see/do than I could possibly list. And I’m sure other dopers can chime in with their personal favorites as well.
Rome -
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[li]Vatican - allow an entire day to see the Vatican Museum and the Sistine Chapel[/li][li]Colosseum - As another poster said in that thread I linked to, buy tickets at Palantine Hill and that will allow you to skip to the head of the line to get into the Coliseum. [/li][li]Forum - I personally didn’t get as much out of Palentine Hill without a good guide. The Roman Forum you can pretty much figure out on your own though. [/li][li]Domus Arias - Nero’s palace has been recently excavated. The entire structure is underground and in a fairly good state of preservation. Fascinating to walk through a structure that has been held in stasis for that long. Just read that it’s closed until at least 2008, so check to see if it’s open before you go[/li][li]Pantheon - Just a breathtaking structure that you must visit. Doesn’t take that long to appriciate, and is just a short walk from Piazza Noavanna. [/li][li]Trevi Fountain - Very tucked away. If it was hard to get to, I’d say skip it, but it’s an easy walk about 2 blocks from the Pantheon. Beautiful. [/li][li]Protostant Cemetary - This is a tad less well know, and will be better gotten to by taking a taxi. Keats and Shelly are buried here. It’s a nice little out of the way attraction that is a bit quieter. A good spot to sit and relax for a bit. Plus the pyramid sticking up is just…interesting. [/li][li]St. Peter’s - This is actually separate from the Vatican. A must see both for it’s pure size, as well as the view available from the top of the dome. Worth waiting in line if you get there early or late and the line is not too terribly long. [/li][/ul]
Florence -
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[li]Galleria dell’Accademia (Academy Gallery) - located in the acheological museum, a must see. Although no photgraphs of David are allowed. [/li][li]Il Duomo(Santa Maria del Fiore) - the main church of Florence. The climb up to the top of the dome was very interesting if somewhat physically challenging. You could both see the artwork on the inside of the dome better, and see a bit of how the dome is constructed. [/li][li] Museo dell’Opera del Duomo(Duomo Works Museum) - right behind the Duemo is this museum. Some great works of art, as well as some of the original stonework from inside the church. There is a breathtaking sculpture of Mary Magdeline that is wonderful. This is a much less populated site, so less crowded. [/li][/ul]
That’s it on my “must see” list. Although there are another dozen things I could add. I wasn’t as taken with Florence, so I’ll leave it up to other dopers to expand on that list.
Venice -
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[li]St. Mark’s Square (Piazza San Marco) - This one section has a lot of things to do/see. St. Marks Basillica and the Doge’s Palace just to name the two big ones. [/li][li]Murano island - lot of glassworks and tons of shops. I’m not a huge fan of shopping on vacation, but there are some nice pieces that you can pick up that make great little gifts. Those $5 necklaces make of Venician glas? Sell for $25 in Las Vegas. So pick up a few things here and there. [/li][li]Music - While you’re feasting your eyes, take an evening and treat your ears to a wonderful performance. The wife and I went to this performance and loved it. A sampling of Vivaldi performed by a quartet in an old church. Only candlelight in the building during the performance. A great evening out and a change from the other sites we saw. [/li][/ul]
One suggestion about Venice. Depending on when you go, what your budget is, it is very nice to have a room overlooking the canal. My wife and I found a great little hotel tucked away off the Acadamia bridge where our room opened up right above the grand canal. We sat on our window ledge and just watched the traffic go by. It was very cool and a great memory of Venice.
Let me know if this help, or if you’d like more information about anything.