I will be going from Positano to Siena in Oct. Is it better to pick up my rental car in Naples or take a train into Rome and drive from there?
If you have another option i would pick it up in florence at train/ bus station or even in siena with avis.
Not ure of your routing but the less u drive the better. Tuscany and umbria is an easy drive butotherwise it can be a bit streesfull.
We took trains from Sorrento (very close to Positano) to Siena and rented a car there. That's what I would recommend. Long day of trains but we love trains (very relaxing, you can read, nap, write in your journal, etc and we always meet fun people on trains) and the scenery is great.
It would be quicker and easier from Positano to go to Salerno and catch a train from there than to go to Naples and catch a train.
Take the shuttle from Positano>Napoli Centrale http://www.amalfishuttle.com/about-us/
Train Napoli Centrale>Chiusi-Chianciano
Rent car at Chiusi station, drive to Siena. Total travel time is around 4 hours.