Itinerary help - Milan to Rome

Trains are an option I would suggest you look into. Lucca is maybe the least 'easy' destination, but it just means one change of train (in Florence). Parking in Siena is difficult - parking really isn't very close to where you want to be. I'd go from Florence to Siena by bus, it's nicer scenery. From Florence to Rome is a little over an hour by Freccia (the high speed train). Driving in Rome would not be my idea of how to end a great vacation. Stay near Piazza Navona or the Pantheon and you can easily walk to just about anything you want to see or do.
My personal choice would be to go directly to Florence for 2 nights. Check train schedules at trenitalia.com. There's plenty to see and do in Florence. Check things out in Milan though and see if that's where you want to spend time. Lucca is a short train ride from Florence. Siena is a beautiful place with great food and lots of wine. If you want, rent a car there for a day or two. Then again, every place in Italy has great food and plenty of wine!

Check allowable blood-alcohol limits in Italy before planning to drink a lot of wine and travel by car, unless one of your party is going to be the designated driver. A quick Google check indicates that it's 0.05%, which may be quite a bit lower than your state's limit. Taking trains would be allow everyone to indulge.

Skip Milan and go immediately to either Siena or Lucca. Add a night to Siena and one to Rome. You do not need a car for this itinerary.

Edited to add you might want a car for your Siena stay so you can wander the countryside but make sure your lodging can arrange parking.

Unless you have tickets to see the Last Supper, there is no real need to stay in Milan.

Rome could easily use another day.

I saw a lot in Milan in a tightly-planned day trip. I arrived by train around 9 am, left my luggage at the station, and took the Metro to the Duomo (walking among the gargoyles on the roof was a fantastic experience). I saw quite a bit after that (Last Supper included) and caught a late afternoon train to Florence. You could do something similar, ending in Lucca that evening.

Google about camera controlled ZTL zones, where non residents can't drive in.

Reading your message I got the idea you are not interested in roaming around the countryside. So why would you drive while trains are faster and may be cheaper? At least avoid the boring drive from Milan to Tuscany; take one of the high speed trains that run under the mountains at 250 kms/h.

Milan has much more than a fading fresco made famous by a writer who missed all his art history classes in high school. The short list includes the Brera Museum, the Duomo with a walk on the roof, the Scala theater, the Sforza Castle, the Gallery and one evening in the Navigli district to take part in the aperitivo tradition (definitely not invented in Milan even if they pretend to believe it).