Rental car return after Tuscany, en route to Varenna

If you don’t want to drive much, dropping the car in Siena is another option. You’d probably need the rental agency to call a taxi to get you to Siena’s train station because the agencies don’t look to be nearby. I think that’s the big factor in which option you choose. My personal preference is to drop the car sooner rather than later.

Where are you picking up the car and which agency (or are you flexible)? Sometimes one agency has a much more convenient location than the others, and which agency has the best location in each city is not consistent.

I can personally vouch for the convenience of Avis-Budget in Chiusi but it’s the wrong direction for your travel.

We're picking the car up at the Rome airport, and will probably use Avis because they have locations at both FLR and LIN and seem to have the best prices. We considered a Siena drop-off, but that would require one additional train leg (Siena>Florence) en route to Varenna, increasing the cost, complexity and total travel time. I don't mind driving on the highways...just trying to avoid the headaches of city driving.

At FLR you can take the tram to SMN station.
At LIN, you can take a direct bus to Centrale.

If you go to LIN, you will also have tolls and gas extra plus it is not as fast as the train. Base fare for the train from SMN to Centrale is 112 EUR for 2 people.

Good point about the extra tolls and fuel, Sam. Sound like if it were you, you'd go the FLR route?

ViaMichelin estimates 55 EUR travel cost including 24 EUR of tolls and 3 hours travel time. Theoretically, you save an hour by train, but that is based on there being an available Freccia when you get to SMN. You should try to make the 11:55 am Freccia or a 12:25 Italo, which is a bit cheaper at 100 EUR Flex Price.

So it is just up to you. Relax on the train for a bit more money or 3 hour drive on the Autostrada.