We are planning to rent a car in Rome (probably at Termini Station location) and drive south to Amalfi. It's a bit daunting to contemplate Rome traffic, ZTL zones, etc.
Has anyone had any experience with picking up a rental car at that location and navigating out of the city to the E45?
Easy peasy.
Just follow this route to the A24 (just look for the green signs to 'Autostrade'), once on the A24 traveling East toward L'Aquila, look for signs to NAPOLI.
It's not the shortest route I could suggest, but it will avoid the city surface streets.
Don't worry about the ZTL there.
If you decide to do this, please come back to this board and this thread and let us know how it worked out for you. (I'm skeptical about this being a good idea, but then I hate renting a car in Italy.) Good luck.
