Rental Car- Rome to Chianti

I've picked up and dropped cars in Rome a number of times, and I think Tiburtino is by far the easiest location if you're heading toward Tuscany. EuRopcar, and probably others, is a quick taxi ride from the station, and the autostrade to Tuscany is very nearby. I've had a few Roman pickups/dropoffs that were way too close to the ZTL, and the Tiburtino area is much less nerve-wracking.

If you are staying near Termini, you might as well pick up there and save yourself a taxi fare to Tiburtina or anywhere else. Termini is not far from Tiburtina anyhow.
If you decide to drive back to the hotel to pick up the luggage after picking up the car, let me know which hotel you are staying and I’ll let you know if it’s outside the ZTL. The Termini station area is outside the ZTL but the ZTL starts nearby west of Via Cavour.
The rental cars are actually in the parking structure on Via Giolitti at the corner with Via Mamiani, next to the Radisson Blu hotel, therefore a bit east of Piazza dei Cinquecento where the station is. Check with the rental counters inside the station (on Via Giolitti side) maybe the day before. I think you may have to go to the Radisson Blu parking to pick up (I’ve only returned there a few times). From the pick up point it is unlikely you will end up inside the ZTL because you are farther and also you will be driving away from it. Simply drive toward Piazza di Porta Maggiore, go around the roundabout then take the underpass toward Viale dello Scalo di San Lorenzo. From there you are on the Tangenziale Tiburtina. Check Google Maps to see the itinerary to the A24 Tangenziale EST. Once on the A24 follow directions to Firenze (Florence).

Thanks for the feedback! We're staying at an airbnb located here: 5 Via Umberto Biancamano, 00185 Roma, Italy. Also, after spending time in Tuscany, we're heading to Positano for 4 nights before heading back to Rome for a couple nights. We've checked out our options (return rental car in Siena or Florence, train from Florence to Sorrento or Naples, then take the public transportation from there to eventually get to Positano. As well as taking bus/train back to Rome from Positano, or even a private transfer, but those are a bit pricey), and are thinking about possibly keeping the rental car, driving to Positano (confirming on-site parking with our airbnb in Positano right now), and then driving back to Rome after our 4 nights in the south (our place in Rome for the last couple of nights is located here: Via Giuseppe Missori, 15, 00165 Roma, Italy). Thoughts on this as well? Thanks in advance!

Your AirBnB is near Porta San Giovanni and far from any ZTL dangers. So if you want, you could drive back to to pick up the rest of your party and the luggage after you get your rental car at the Giolitti Parking next to the Radisson Blu. To go to the Radisson from your apartment it’s less than 20 min walk, so easily doable without luggage. The area where your apartment is has limited street parking, so when you go back to pick up parents and luggage make sure they are downstairs ready to go because you may have to park in front of a driveway or even double park while you load the car.

Regarding driving to Positano, I would drive to it, especially if your place there has free parking. You talked about having parents with you, so I presume there are at least 3 of you and I don’t know if your parents are elderly. Going to Positano from Tuscany with public transportation implies multiple means of transport (high speed trains, commuter trains, and a bus) and that is too much trouble, especially if traveling with older folks. Once in Positano, given the traffic and the scarce parking, you might find that it is better to leave the car parked at your place the whole time and use buses and boats instead, but having a car to get there and out of there is convenient IMO. If your Positano AirBnB has no parking, there are a few pay parking lots in Positano (I’m sure your host will suggest the closest if necessary). Public parking is not cheap in the Amalfi coast, so get ready to pay at least 3€ per hour for short term parking and up to about 25€ for the full day. So if your landlord has free parking, that would be super.

Thanks Roberto, your advice is very reassuring! So you still recommend Roma Termini to pick up the rental car? Also, based on where I said our 2nd Rome Airbnb is, where do you recommend dropping the car off on our way back from Positano?

Yes, pick up at Termini.

For the car return.
I’m assuming you will be renting from either Hertz or Europcar, since they usually have the best prices on www.autoeurope.com, the consolidator’s website most of us here use to rent cars.
Depending on which of the two companies you use, these are the closest locations to your second apartment near the Vatican (actually near the San Pietro train station.

Hertz - Roma Vaticano
Via dell'Argilla, 5, 00165 Roma RM, Italy
+39 06 3937 8808
https://goo.gl/maps/qqk8o7zbj1N2

Europcar ROME VIA CIPRO (VATICAN)
Viale degli Ammiragli, 107, 00136 Roma RM, Italy
+39 06 3972 0639
https://goo.gl/maps/TP1JUS76Rfo

From either you might need a taxi to your apartment if you have luggage, otherwise it is a walk (doable though without luggage)

To get to the above addresses, or to your apartment, I recommend you loop around on a clockwise fashion on the G.R.A. (grand ring beltway) A90 coming from Naples, so that you approach the area from the west, to minimize city street driving. Try to exit the A90 beltway at the Via Aurelia (SS1) exit (that is the GRA exit no. 1), located west of the city, then drive east toward either location. Use your navigator on your phone, but make sure you go to that exit first, then drive east on the Via Aurelia.

If you return to Rome on a Sunday, the car rental offices above may be closed.
In that case, drive and return your car to Fiumicino airport. From there you can take a taxi to your apartment (about 50€) or you can take regional trains from the airport station to Roma San Pietro station. One train change is necessary at Roma Trastevere station, but from Roma Trastevere to San Pietro it is one stop only. Your apartment is walking distance from the San Pietro station.

Also in this case you might want to drop luggage and passengers at the apartment, then return the car, the area is not in the ZTL. It’s up to you, just program the addresses in your GPS.