Bolgheri/ San Gimignano
This is as different from the rest of Tuscany as can be. Start from the many-towered town of San Gimignano (it had fifty-two towers in its twelfth-century heyday, riches mostly gained from cultivating saffron). To me, what is more impressive are its many small piazzas, and its pale Vernaccia wine. Head to Volterra, one of the most important sites of the Etruscans, then southwest down to the Bolgheri region. This is the home of remarkable blends like Sassicaia and Ornellaia. Lunch on the seashore at La Pineta, (hidden in the pines at Marina Di Bibbona). Such a lunch merits a restful afternoon; best to stay in the area overnight. Head back east through Massa Marittima on the road of your choice. All roads here are wonderful for wandering.