When and where to rent car? 5 travelers

If you are going straight from Rome to the Cinque Terre without making stops to visit the areas in between, you may not need a car at all. I understand that 5 train tickets from Rome to the Cinque Terre may be a substantial amount, but once you add the daily car rental plus gas and tolls, a car may not be that much cheaper. Also there are cheaper trains that travel along the coast. Rent a car if you plan to visit places along the way for a few days, but otherwise I would reconsider.
You could rent in Rome and return to La Spezia. The coastal route is generally less congested and shorter.

Train to Orvieto and pick up your rental car there. It's an hour outside of Rome, so you don't have to deal with all the city traffic.

We rented a car in Padua and dropped it at La Spezia before going to the Cinque Terre. We loved having a car to drive around the countryside, but I will tell you that La Spezia was not easy to drive in. It took us a lot of "do-overs" to find the car rental agency, and then they added some sort of a tax to our bill. There was no arguing with them, as they just escorted us out the door.

We have rented cars twice in Rome, and then took off from there. We did not have a problem either time. The last time we got one at the airport and headed to our B&B's in Umbria and Tuscany. We used the car to take day trips to explore the area. Bring your GPS from home, your drivers license and IDP, and a Michelin map of Italy. For 5 people it will be quite helpful if you minimize your luggage!Check each and every city that you may drive in for maps of their ZTL's. Check out rates and pick-up and drop off options on the the Autoeurope.com web site, and also look at the options that Kayak,etc will provide.

Good luck with a car big enough for 5 people AND too much luggage. Save yourself the headache and just take the train.