First trip to Italy

On arrival, hop on train to Florence for two-three days. Then pick up a car (where TBD according to the places you choose), explre from one or two bases in Tuscany, then last drop the car and return to Rome for last four or so nights. That way, there is no need to split your stay in Rome.
You have a surprisingly high number of places to choose from in Tuscany, so I would continue reading to narrow that down before deciding anything else. You might read up on wine areas first since you expressed in interest in that.

• Does it make sense to rent a car in Tuscany?
YES

• Any recommendations for hotels? (it is just two adults)
WHERE?

• Feedback/suggestions on the itinerary or things to do? We enjoy wine, fine dining. We have booked fights in an out of Rome so we are pretty flexible.
SIENA PROVINCE: Siena, San Gimignano, Monteriggioni, Val D'Orcia (Montepulciano, Pienza, Montalcino, Buonconvento, Montalcino), Chianti Road, If you stay near Siena, you will have access to the freeways. You can even reach Cortona in less than 90 min.

If you have to fly home from Rome, make Rome your last stop, not the first. Simplifies going home.

I would also agree if flying home from Rome to make Rome your last stop. Your itinerary idea is similar to our first trip to Italy many years ago. The only difference was that we were on a tour and included Umbria. When we arrived in Rome we took the train to Florence where our tour began. Roberto’s suggestions are great if you are renting a car.

Some of our favorite stops- Lucca, Siena, San Gimignano, Volterra, Montepulciano, Montalcino, Gubbio, Cortona, Assisi, Spello, Todi, Orvieto, Civita di Bagnoregio. Lots of choices!

Hey Cindy! Welcome to the forum!

That sounds like a great trip. Based on our experience, this is what I suggest.

As mentioned, take the express train to Florence on arrival. Spend the next two days (at least) in Florence. You won't want/need a car in Florence. Then rent a car and stay at an agriturismo in the Tuscan countryside. We stayed at Castillo di Verrazzano, just outside Greve. From your agriturismo you can explore Tuscany. Return to Florence and take the express back to Rome for the end of your trip.

Be sure to study the rules of the road and the signage before you go. Most hill towns have ZTLs where you can't drive, but there's ample parking outside the ZTLs. Assume anywhere within the walls is ZTL. Driving in Tuscany is fun and easy, just be sure to strictly obey the speed limit. They have automated speed detection systems.

Welcome to the forum Cindy!

Rome, Florence and the Tuscan countryside is a perfect first trip to Italy.
A car is almost required for exploration of the Tuscan countryside- so yes- makes sense. Hopefully rates have come down a bit as they have been off the charts this year. (If not then only get the car for the days you really need)
Do your homework on driving in Italy and be sure all drivers have their IDP- International Driving Permit- required by law - and driving is quite enjoyable in the region- BUT not in the larger towns/cities (ZTL, parking, etc)
This is good info even if a bit dated:
http://driventoit.blogspot.com/2015/01/driving-in-italy-including-dreaded-ztls.html

You can get your IDP at your local AAA for about $20.
We always rent thru www.autoeurope.com- usually best rates and awesome customer service.

Head to Florence first- and since that first day is jet lag I’d give it 3 nights.
Then pick up your car as you leave Florence (lots of posts on this topic, a search will bring up all sorts of info on how/where- look for posts by Roberto and his helpful directions)

I’d pick 2 locations in Tuscany- somewhere in the Chianti region or even Siena works well, then somewhere further south in the Val d’Orcia region (Montepulciano is our favorite).
Split those stays 3 and 4 nights or 3 and 3 nights
You can then drop your car in Chiusi or Orvieto- (no need to return to Florence) and take train to Rome.
Orvieto is a beautiful hill town that is worth a night or 2 as well (Umbria, not Tuscany)
Don’t be afraid to give Rome 5 nights. You will never run out of things to do in the Eternal City. We spent 5 nights in Rome on our first trip and have since returned 3 times, still not done!

Some people do like agriturismo stays, but we prefer to stay in town as we love the atmosphere in the evenings when crowds are gone and we like to drink wine with dinner so don’t want to be stuck on a farm/villa in the countryside for all of our dinners. YMMV

Make sure your lodgings provide easy to access parking, you will mostly be parking outside the wall of any hill town.

Once you decide on your itinerary we can offer lots of recommendations for lodging, restaurants, tours, etc.

It looks like you have 15 nights in Italy, is that correct?

Itinerary would look like this:
Fly to Rome
Train to Florence- there is one direct train from FCO each day to Florence at 1:53- great if you can catch that otherwise train to Termini then change to train to Florence.

Florence 3 nights
Get car
Tuscan town #1 3 nights
Tuscan town #2 3 nights
Drop car
Orvieto 1 or 2 nights- (I’m throwing this in because we loved it so much and it is a good car drop off place Hertz only) ;)
Rome 4 or 5 nights
Fly home

Get RS guide books, they are full of info, logistics, etc.

Have you driven in other countries in Europe? It's not at all like driving in the US. Be sure to have some kind of GPS. I used a Garmin and google maps on my phone. I sometimes got conflicting directions and the signage (when there was any) wasn't always helpful. Note everything Christine wrote, especially about drinking. The legal limit in Italy is 0.05% (in the US it's 0.08%) which is the difference between one glass and two. If you want to spend a day visiting wineries and doing tastings, you should take a small group tour or private guide, which would probably be cheaper than car rental anyway. Most towns are hill towns, and you can't drive into them. You have to park below the historic center and walk up. Parking is limited and you may have to pay, using a machine to buy a parking ticket. Because Tuscany is hilly, roads are winding and often narrow, sometimes not in good repair. One more thing, you may be there during the grape harvest. I imagine it would be a very good experience. However, it can also mean slow going on the roads if you end up behind a truck full of grapes.

While it will limit your choices, you can get around by bus and train, using larger towns as bases. Florence is very good because the train/bus station is on the edge of the historic center

Thank you all for providing me with so much information for our first trip to Italy! I have spent most of the day researching your ideas and have come up with an itinerary, based on ChristineH's suggestions. Now I would like to request any recommendations for lodging, restaurants, or tours in Siena and Montepulciano. Lodging in agriturismos or in towns would be most appreciated while we a driving around Tuscany. We might possibly do a combination of both.
Hotel recommendations in Rome would also be great!!!
Once again, I appreciate your insight!!!!!
Cindy

Cindy- Glad you found info here useful and are on your way with the planning- that’s just as much fun as the trip!

I’ll assume you will have a car and need parking in Tuscany locations
These are the places we have stayed- all have easy access parking, either on site or nearby- I would return to any of them.

Siena-
Hotel Palazzo Ravizza- fabulous views from their terrace, just steps to center/Il Campo.
Parking is just below/behind the hotel and is secure
https://palazzoravizza.it/en/

Just next door is Hotel Athena. Same view from their terrace.
https://www.hotelathena.com/en/

Montepulciano
Palazzo Carletti- beautiful old palazzo, beautiful frescoed rooms. Parking is just below the hotel outside the walls, fairly easy to get in and out for day trips
https://www.palazzocarletti.it/en

Pienza-
Piccolo Hotel a Valle
We chose to stay here this past May- Pienza is a flat hill town, very small, very charming, great location for exploring Tuscany. This hotel is pretty plain, nothing fancy but the room with balcony had a FABULOUS view. Parking was on property- super easy, very nice staff. Just outside the walls, walk into village is about 1 minute.
https://www.piccolohotellavalle.net/en/home/

Florence
Hotel Berchielli
Stayed here this past May- right on the Arno with views of Ponte Vecchio. Easy walk to everywhere. Lovely staff, great breakfast, very comfortable rooms.
https://www.berchielli.it/en/

I would get started looking and booking. September is a busy month!
I use booking.com for all my lodging research and do book mostly with booking.com as I get better discounts.
You can filter according to your needs, budget, location. You will want air conditioning! Read the reviews there- they can only be given by folks who have actually stayed so you can trust them.
I never book anything that is prepaid and not cancellable- especially in these uncertain travel times.

Hi, Cindy! We just returned a few weeks ago from our second trip to Italy in the past five years. Definitely rent a car for Tuscany!

In Rome, we recently stayed at both Hotel Damaso and Hotel Artemide. They are both great. Damaso is right between campo di fiori and Piazza Navona…a great location for a first time visit. Artemide is closer to the train station and Monti. Both offer a complimentary full breakfast buffet. In Tuscany, we spent five days at Terre di Nano, between Montepulciano and Pienza. It was the definite highlight of our first trip.

In Florence, we enjoyed Hotel Davanzanti. Breakfast and happy hour, great location, fun staff.

We too like fine dining, but in Italy we prefer the more traditional trattorias featuring classic dishes. Highly recommend Ditirambo near Campo di Fiori for a unique spin on the classics. Check out Elizabeth Minchilli’s website for her favorites throughout Italy. She has not steered us wrong yet!

In Rome, we really enjoyed our food tour of Testaccio. It’s the only touristy thing we really did this trip and it was delicious plus we learned a lot!

Happy to offer more suggestions!