Rental car drop off in or close to Rome

Where are you staying in Rome and which company you are renting from? All rental companies have multiple locations in Rome.
Termini is one of the few places (maybe the only one in the city) where all rental companies use the same multistory car park structure.
Termini is not hard to reach coming from Tuscany.
I usually go to this rest stop to fuel the car before returning to Termini. It's on the freeway on the tangenziale Est, therefore you will reach it without having to exit to city surface streets. Save it as your first destination coming from Tuscany.
https://maps.app.goo.gl/JWJFVW7KMtCGyiFP7

From that rest stop location I then return to Termini taking this route:
https://maps.app.goo.gl/kSyJP2iiULa23rUq7

Very easy. Just verify your company uses the ES Giolitti Interpark Garage, because some have started to use the Termini garage below, across the station on Via Marsala:
https://maps.app.goo.gl/oeqXhqBRtc9MXW6T9

The route would be the same (actually easier since from Via Marsala you don't need to drive the underpass road under the station to Via Giolitti.

Thanks so much for the detailed reply. We haven't booked a car yet as we weren't sure where to return it to. You have alleviated my worries about filling up with gas and driving to the Termini drop off. My husband is a good driver so everything should be fine. Really appreciate all the links and advice.

Many thanks!☺️

Maybe drop off at FCO airport, then Leonardo Express to Termini. There are good signs for getting to FCO from the north (not so good leaving FCO).