Tuscan drive - Como to Siena

Lake Como to Siena is about a 6 hour drive even on the expressways, so I would tempted to take the expressways to either Parma, Modena or Bologna (all great food cities with worthwhile sights to visit), have lunch and spend the afternoon in the city of your choice, take the expressways to Florence and then the scenic SR222 through Chianti to Siena (if you still have the time and energy). There are small towns along SR222 where you could stop for dinner if you wish, although you'd need to confirm a late arrival with your villa.

My advice would be to take the train. Driving can be a hassle and confusing for tourists. Hope this helps!

Parker - A fairly fast route leaving from Lake Como would be A-9 to A-50 to E-35. However, if you'd like some great scenery, once you get near Florence get on SR 222 route, just a little south of Florence. It's called the Chianti Road, and it's a very scenic drive once you get a little more south of Florence. You'll go through Greve and Castellina, great Chianti towns and a place to get lunch or a snack. As you continue south you'll come into Siena on SR2 route.

Buonconvento, Italy is a gem just 30 minutes from Siena and worth visiting. It's a wonderful little town. Another town worth a stopover along the way is San Quirico d'Orcia, Italy.

Buon viaggio!

In the real world the E-35 should be the A1 from Milan to Naples.

I doubt following the signs saying "A1 Bologna-Roma-Napoli" till you see an exit sign saying "Siena" will be confusing, that's not a problem. It's just that a train would be faster and that you'll have luggage in the trunk.

A car around the Lake is pointless for most tourists. Ferries are easier and faster, with better views.

Along the way there are tons of sites and medieval (more or less) towns, each with its own camera controlled ZTL area to keep tourists' cars out of the historic center. So you'll have to park out of the center, hide your stuff and walk. Is this ok for both of you? Are you going to pay for a full coverage in case of a car break -in?

There are also to the mountains along the way.

Another option would be to take the train to Florence, rent the car there and spend the rest of the day slowly working your way down SR222 to Siena, perhaps detouring to visit the American (WWII) Cemetery.