Holly, we visited this area two years ago and will return a just a week or to after you guys visit (first week of October). MUSTS: depends what you like, or course. We plan to explore mostly new sites, but we will return to two of our absolute favorites: Loches and Chaumont sur Loire. Loches is an entire village built around the base of this walled compound of castles/church/homes/etc. You get to explore it at your own rate. We could have stayed there all day. We did have both lunch and dinner in the village outsid eof the main gate. Chaumont-sur-Loire was the whole enchilada... I guess in France is would be the whole crepe. Beautiful castle, exceptional setting and landscaping/gardens. Plenty of elbow-room to explore at your own pace.
As you explore this area of France we will give you some advice we wish we had been told. NOTHING seems to be open after 6 pm and on all day Sundays. So if you want to return back home after being gone all day, and want to hit the grocery store to pick up dinner... if it's after 6, it's most likely going to be closed. The BIG grocery near us had its lights off and doors locked with a woman letting people out, but not in, at 6:15... and they were closing at 6:30! On Sunday we found ONE restaurant which was open... every place else was closed.
the other bit of advice, when you rent your car BE SURE TO GET A GPS! I am excellent at map-reading and for those of you know what I mean, "I've never been down this road before, but I know exactly where I am" , the GPS was heaven sent. Not that I didn't know where to go... but the little villages you will run into and have to wind your way through to get to the other side to continue on... well they weren't meant for cars and are utterly frustrating to get through. But, follow the GPS path and Voila, you're through and a saved marriage on the other side. It really took a stressor out of the vacation and I will absolutely rent a car with this again.
Final advice, I don't know when in Sept you're going, but the 2nd or 3rd weekend of Sept is European Heritage Days. During this long weekend, there are many castles, abby's, follies, etc which are never open to the public are open then. We visited two privately owned castles... L'islette and Gue Pean... neat!
okay one more. Amboise castle has a village of resturants at its base. We went there for dinner and LOVED IT! The warm sunset illuminated the tall fortress walls on the other side of the street, and the swallows were flying in and dicing into their nests. The restuarants made it feel like Paris! they even had "Amorino" gelato there... oh God now I really want to be there and now wait half a year!