kelli,
A few thoughts regarding your questions.....
To begin with, have you considered travel by train rather than rental car. Keep in mind that each driver will require the compulsory International Driver's Permit, which is used in conjunction with your home D.L. You'll also have to be VERY careful to avoid the dreaded ZTL (limited traffic zones) that exist in many Italian towns of all sizes. There are also the issues of high parking costs, tolls on some roads, high fuel costs and the fact that your magnetic stripe credit card may not work at automated (unattended) fuel pumps. You'll also have to budget for at least some of the rental car insurance as it's compulsory to purchase CDW and theft insurance from the rental agency in Italy. Travel by car will not be as quick or efficient as using the high speed trains which run on the main routes (they travel at up to 300 kmH).
Onto your questions.....
- Siena would be a great place to stay in Tuscany. It's a wonderful and historic city, lots of great restaurants and good hotels. If you'd prefer a larger location for a few days, you might consider staying in Florence (which is also in Tuscany) and take a day trip by Bus to Siena. When are you planning to be there? You may have difficulty finding a hotel during the Palio in July and August.
- If you feel that you absolutely must have a car, you could consider returning it in Siena. You might find it helpful to contact THIS firm and discuss car rental. They'll be able to provide lots of good information.
- The "best way" (IMO) to get from the Cinque Terre to Venice is by train. It will be about a six hour trip with several changes. The usual two routes either go through Milan or Florence. Once you reach either of those cities, the last leg will be via Freccia high speed train. Note that your destination station will be Venezia S. Lucia. You can research the various rail options using the Trenitalia or bahn.de websites.
As you're "completely new to European travel", it would probably also be a good idea to mention that there are some "caveats" with using the trains in Italy (that includes Buses and transit in Rome, etc.). If you're using Regionale trains (such as the Leonardo Express from the airport), you MUST validate (time & date stamp) the tickets prior to boarding the train on the day of travel. Those found with unvalidated tickets will face hefty fines which will be collected on the spot. If you're using the "premium" trains such as the Freccia high speed trains, note that tickets are specific to a particular train, date and departure time. You MUST only board the train specified on the ticket, or once again you'll face hefty fines *** collected on the spot***!
Happy travels!