2 weeks, 2 bases in Tuscany?

Will you have car(s)? Or will you rely on public transport? If relying on Public transport I wouldn't stay in a small town, Florence is one base. The other base depends on which part of Tuscany you prefer to visit. For Western Tuscany, Pisa is the most linked in terms of transportation. If you have your own car(s), then the options are infinite. The best option for 6 adults is probably two agriturismo (farmhouses) located not far from the main Tuscan freeways. Agriturismos offer better accommodations for the price, no parking issues, privacy and wonderful amenities at a better price.
If you have cars, one base should probably be anywhere between the Florence and Siena corridor, not too far from the Autopalio freeway (that will give you access to several small towns of interest, plus Florence, Chianti etc). The other probably should be in the Pisa or Lucca provinces, That will give you easy access to the Coast, Apuana mountains, Cinque Terre. For a more rural environ you may be interested in the Maremma area too, in Southern Tuscany in the Grosseto province. In that case you'd choose a place near Grosseto. If you want to stay with "the locals", instead of on your own in a farmhouse, then choose any towns (get a Rick Steve's book for suggestions) in the two areas I mentioned above.

Good advice...thanks. Have written it down. We definitely have a car. a couple want to bike...no problem with that right?

We stayed at Il Canto Del Sole. It was the most amazing place in Italy we have every stayed. The location in the Tuscany region was perfect. About 10 min south of Siena and 30-40 min to all the hill towns. I would highly recommend a week in this area.

Tuscany is the Mecca of bikers, both road bikers and mountain bikers. You'll see tons of them if the weather is nice, especially on weekends. Just be careful sharing the road because roads are narrower than in the US and cars will pass you and zip along dangerously close to you. So keep the right. There are lots of websites for agriturismo offers. Two of them are below: www.agriturismo.net
www.agriturismo.it In your situation (6 people traveling together visiting the same area for at least a week at a time) I wouldn't do it any other way. The savings are huge for a big group. Some agriturismi even serve food in others you cook in your own kitchen. Just make sure you know the exact location of the agriturismo before you book one. Some might not be easily accessible or close to the main thoroughfares. Consider that driving in Tuscan country roads may take longer than it looks on a map. So check the exact locations and distances (and travel times) on google maps. Once I took some American acquaintances to a farmhouse they rented in the Chianti that entailed a 2.5 mile unpaved driveway through the grapevines. It took me half hour just to drive the driveway from the highway to the house.

Was thinking about Cretaoile although they are booking up pretty fast.
Thanks for the biking advice..you won't be getting me on one of those.

Step #1 = Read about Tuscany (Rick Steve's book?) and what towns, cities, areas you want to visit during the 2 weeks. You won't be able to see everything, so you have to choose just a few. For visiting Florence plan at a minimum of 2 or 3 days. Siena, Pisa and Lucca, will take at least 1 day trip each (Pisa+Lucca might be squeezed into one, but that would be rushing it). All other smaller towns, you might be able to squeeze 2 or 3 in a day if they are close to each other. Step #2: Once you have plotted on a map the places you want to visit, go to Agriturismo.net (or .it) and search an agriturismo in one or two base locations that are central enough to the area where the places you'll be visiting are. Some Agriturismi are huge, however most have been divided into separate small apartments within the farmhouses and the converted stables. You don't need to book the whole farm complex which might sleep 40 or 50 people if there is only 6 of you. Cretaiole is only one of thousands of agriturismi in Tuscany. It's located in the Val d'Orcia south of Siena. If that is where you want to stay, fine. But don't worry if you can't get that one. There are thousands to choose from, many in the Val d'Orcia itself. You've got one year to go. You can start reading on your spare time. No rush. October is not the high season, therefore most places don't sell out that quickly.

Just in case cost is a big factor for you; Agritourismos are not always particularly cheap. They often provide some great meals, but only at a premium price - and with no cooking facilities of your own, you will have few options other that partaking in their meals. I'm sure there is a great amount of variation in price, but I wouldn't be surprised to have the costs (with dinner) work out to something like 70-100 euro per person per night. As an alternative if costs matter to your group; You can rent an apartment/cottage. There are many choices out there. The one we used this past summer was located just a few miles southeast of Siena in a setting so quintessentially Tuscan we felt like we never had to leave it to experience everything we were looking for in Tuscany. For our entire family of five, it cost 100 euro per night and had a pool, too. We made our own meals. Unfortunately our place could not sleep six or I would be happy to recommend it to you.

Cost is not the main factor. Quality and ambiance is for us.

Think about renting a villa for one or both of the weeks. Go to VRBO to look into. With 6 people, you could probably find a pretty awesome place with a pool for less than what you might spend per night per couple at a higher end agriturismo. If you stay close enough to a small town, you could still go out to eat, and not feel like you had to cook in. Last year my husband and I rented a farmhouse with a great view, pool, about 5 km from Cortona and loved spending late afternoons or evenings by the pool with a bottle of wine. To someone's point earlier, make sure you aren't situated 30 minutes away from a main road as that would get old quickly.
Perhaps spend one week along the A1 Corridor where you could easily take the train into Florence for a day or two, visit Umbria, Sienna, Montalpuchiano, Cortona, or Assisi, then another week a bit further west.

Those two websites give you all types of accommodations, incl. hotels, bed and breakfast, apartments, apartments in villas, farmhouses etc. Agriturismo is sort of a generic term for all types of farmhouse accommodations but there are big variations in the type of service arrangements and amenities included (and prices). Not all agriturismos offer food and in any case even when they do, you are not obligated to eat there every meal (or any meal at all). However 6 adults (is it 3 couples?) would likely save with a farmhouse/apartment accommodation in the countryside over renting 3 separate rooms at a hotel. Besides, the experience itself of living in an Italian rustic home will be memorable.
PS: if you see a scorpion in the countryside don't panic. Italian scorpions are harmless.

Scorpions? In Italy?? thinking renting a villa for 6 might be the way to do it. Thought the concept of having breakfast made and more of a sense of community would be good though. Will look at both ideas...

I like Siena as a base and for biking. you can see about 6 blockbuster villages nrby.
Assisi is nice as a base for Umbria.

annemarie,
This will give you some ideas http://www.slowtrav.com/italy/tuscany/hs_planning.htm

Annamarie, as I write this I am sitting outside my door at Villa Mazzi looking at a beautiful view of Montepulciano. Please google it and consider at least for one week. They do not serve meals but the facilities and the location are superb. Montalcino, Pienza, Cortona, and many other beautiful sites are close by. Loredona is a great hostess and she has many items that they produce such as wine, olive oil, honey and jams. I highly recommend it.

Annemarie, we are just now settling into our hotel in Florence after.a three day walking tour of the Etruscan necropolis sights in the Maremma region. It was an awesome total immersion experience and I recommend the area highly. Great people, stories, and vistas. Do a search for images of Pitigliano and Sorano. We stayed in a B&B in the fortress at Sorano. What N experience and the food was all regional and delicious.