I don’t suppose you rent out as a chauffeur?? 
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 -
[ul]
[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 -
[ul]
[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 -
[ul]
[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.
Very helpful. Everything you mentioned sounds exactly like what I want to see.
Obviously, I agree with shelbo. 90% of what’s worth visiting in Tuscany will be out of reach without a car - and to give short shrift to Tuscany would be a heinous crime. Only in Rome did I find the drivers seriously attempting to live up to the Italian stereotype - even Florence was no big deal.
In fact, I found that flinging a small car over the Tuscan hills and around its curves was a hoot (Italians approve of spirited driving). But perhaps best of all were the small, out-of-the-way restaurants, which really are among the most enjoyable places to eat on this planet (and almost entirely unvisited by train passengers).
Thanks, Xema. I only wish I could realize my fondest dream…rent a small house there for a month or two.
IMHO - take me. We can explore together.
StG
I’d go back in a second.
I found the website of the place I stayed for about a week: La Sovana (it’s looking a bit fancier than I remember it). It’s a sort of country villa (once was a farm, no doubt). I did day trips to all sorts of interesting spots, and had barely scratched the surface when it was time to move on.
My best advice is–if you’re in a major city–to get out of the touristy areas. If you go to Venice, just get lost; it’s much more interesting than just going to St. Mark’s and “seeing the sights”. I’ve never driven in Italy, so I can’t offer much perspective there.
I disagree. If you want to see what a Roman city looked like, go to Pompeii. If you want to see incredibly well preserved art and architecture, go to Herculaneum. Pompeii is larger, but is not nearly as well preserved as Herculaneum. I recommend seeing both.
I’m relatively certain that you can’t drive from Sicily to Naples. 
I drove there extensively.
Taking one of these with an inline 2-cylinder engine down an autostrada onramp is either an exercise in bravery or stupidity.
I was a younger man then. Whether I was braver or more stupid I still haven’t figured out.
I should mention that if you plan to visit Capri, and take the bus from Capri to Anacapri, I hope you have a strong constitution. Riding a bus as it flew around a hairpin turn at 40mph, with another bus passing in the other direction, on a road which was barely wide enough for one bus, and which overhung a 100-foot-or-so cliff, was, to say the least, exciting.
(Man that was a lot of commas.)
StGermain, if I ever win the lottery, you are on! 
fachverwirrt, I can relate. The highway from Durango to Ouray in Colorado ain’t no cakewalk. :eek:
Mr. Moto, funny, we were joking about doing it on Vespas. ::doofus smiley::
Thank you, everyone, for all the great advice. I think I am pointed in the right direction now.
Except that if it’s your first and possibly only trip, you really should go see those major sites. There’s a reason everyone wants to see them. They’re impressive, beautiful, and full of history. Sure if it’s your 3rd or 4th time I’d recommend getting off the beaten path, but your 1st trip? I mean…your first trip to Rome, and you didn’t see St. Peter’s or the Coloseum?
Yeah, after I posted that I thought about it a tad more. You’re right, the sites are different enough that you’re not really seeing the same things. Plus, with Pompeii now they’re doing so much “reconstruction” that it’s losing it’s appeal of being in the same state as it was found. After a certain point, restoration = basically new building.
I’ll assume that you know there’s a car ferry and are just teasing. But for anyone that doesn’t know there is a very large car ferry that runs across the straights of Messina constantly. So while you can’t drive over a bridge from Sicily, you can have the same car and drive from Sicily to anyplace else in Italy…and vice versa. Just don’t want anyone confused.
Hell, you can take the train from Sicily to Naples. I’ve done it.
They disconnect the engine and roll the cars onto a ferry with tracks embedded on the deck. In Messina, the train is reassembled and you are on your way. During the crossing you can stay put in your seat, or have coffee and pastry in the ferry cafe.
When my folks went to Italy, they would rent a car and just take it from there. They never planned out where they were going to stay or how long they would stay. They did this several times and I never heard my father complain about the driving. That being said, he was always a somewhat aggressive driver here with good reflexes so YMMV.
Oh, definitely. But if you have enough time, get away from the touristy areas after you’ve seen them. Don’t eat in St. Mark’s square, for instance; you’ll find food for a fraction of the price if you wander off somewhere else.
The most dramatic example of price differences between touristy areas and non-touristy areas: at a random little store in Rimini, I got a 2 liter bottle of water for 750 lire. At the Boboli Gardens, I got a 1/8 liter bottle of water for 5000 lire.
Yup, just teasing. 
The key to good value in food is to go where the restaurants can’t survive principally on tourists. The places where locals eat will almost always have better food for less money.
Okay, I get that you want to find places to eat out of the touristy areas, but what can I expect will be “normal” (to Italians) on the menu?
Italians typically don’t eat much breakfast - they grab coffee and bread or pastry on the way to work. That’s pretty cheap right there.
Lunch and dinner are more elaborate. Dinner is eaten late by American standards.
The typical Italian meal has a first course of pasta, a main course of meat, a small salad, water, wine, a small dessert, and coffee. If you go to a trattoria instead of a ristorante, you’ll find a smaller, more casual establishment with a more limited menu. These also have great food for the most part.
Generally, full dinners in these places would come in at less than $20 when I was there. Don’t know about now, but it won’t be much more.
If you want to economize further, you can substitute sandwiches and pizza for many meals. But I think you’ll find food won’t be your biggest expense.