We are looking forward to spending around 10 days in Puglia before joining friends that rented a villa near Florence on June 1. We plan to fly into Puglia (probably Bari), rent a car and stay at 2 locations with day trips .

Our biggest decision is how to get from Puglia to Tuscany. One choice is to drive and spend the night somewhere around halfway. Does anyone have a suggestion of what might be an interesting small town to stay in with an easy drive. Or do you think better to fly from Puglia to Florence and rent a second car to use during our time in Tuscany.

We could also like some ideas of the two best areas to stay in to enjoy many of the treasures of Puglia.

Moved to Europe board

I would drive and use the opportunity to see another part of Italy. The drive is pretty easy with a straight shot autostrada most of the way. The Bologna-Florence section goes through the mountains and carries a lot of traffic, but it's in good condition. Look at Ravenna as a stop-over, it's an easy city and the mosaics are amazing. From Puglia, don't miss Matera, it's one of Italy's most amazing sights.

We spent a week in Puglia a couple years ago, and our trip report is here: 7 days/6 nights in Puglia

We especially loved Lecce as our southern base. Although we stayed in a trull home out in the country, since we always dreamed of staying in one. If we returned, our northern base would probably be Ostuni or Monopoli. And, if you have enough time, we second the recommendation to go to Matera (in Basilicata not Puglia), one of favorite spots in all of Italy.

There aren't a lot of great choices along the highway, without a long detour. Rome might be close to your halfway point. Maybe a little further north to Orvieto? I think we would consider flying from Bari to Florence. Most people would not keep a rental car in Florence, but it would be nice to have one for some trips within the Tuscan countryside. I would try what I could do by rail (Siena, Pisa, Lucca, and many others) and maybe rent a second car for whatever number of days you might want to go to more remote areas. We often rent multiple cars when in Italy and find that it is not much more expensive per day doing it that way. Also, I suggest you consider AutoEurope, a highly regarded broker which generally has great rates plus a reasonable daily insurance charge that can be a fraction of the cost through a rental agency at the desk.

I agree with HappyTrvlr and I also recommend spending a night or two in Matera if you can. And since you are flying into Bari, you could make it one of your bases.

There are tons of gems in Abruzzo, Molise and Umbria. But if you have only 2 days, it's not worth to try to visit them.
In this case, you best take the motorway via Chieti - Tivoli if you come from Foggia/Gargano or via Avellino - Caserta if you come from Bari.
There is only 1 direct flight between Apulia and Tuscany, with arrival at Pisa towards midnight.
A train ride from Foggia to Florence lasts 4 3/4 to 5 1/4 hrs.

Thank you all. We will plan to go to Matera and then drive to Salerno for a fast train to Florence

Oh, Salerno is, IMO, vastly underrated! And it's the perfect place from which to visit magnificent Paestum.