Cinque Terre to Siena

Efficient is an interesting word as used here. I'm not sure what you mean by efficient. If by train, you are looking at a 3.5hr journey with 2-3 train changes (La Spezia, Pisa and Empoli). If you go via Florence, you'll spend about the same amount of travel time and make about the same number of train changes. One alternative is the bus between Pisa airport and Siena. It takes about 1.5hrs to get to the airport and another 1.5hrs on the bus. Overall, you're still lookiing at about 3.5hrs.

Nels, Rather than "mix" different modes of transport, I'd suggest travel by train as the "most efficient" method on that route. As the previous reply indicated, there are usually two changes at Pisa and Empoli. The shortest travel time seems to be a train that departs La Spezia Centrale at 12:20, arriving Siena at 15:14 (time 2H:54M). The longest time appears to be 3H:26M. Current second class fare is listed at €10.90. When you arrive at Siena, you'll need to take a Taxi or Bus up to the city (the rail station is at the bottom of the hill). Happy travels!