Five or six days in South of France or Germany/Alsace?

Lyon is interesting place; worth a visit; the old town is a UNESCO world heritage site.
Nice; the views over the old town and beach area wonderful; If you like Matisse and Chagall there are museums for each artist there.
Avignon could be a daytrip place or like Aix used to explore the Provence area so you do not change hotels a lot.

Since you have six days that should cover it. forget Alsace for now since you mentioned it second.

I haven't been to Switzerland or eastern Germany recently, but I visited all the French areas you mentioned earlier this summer. Any one of them would be good for the amount of time you have, but you'd spend more time getting to and from Nice by train. But the weather might be nicer along the Riviera.

One thing I'd caution you about is that cute small towns in southern France and Alsace tend to be swamped with tourists, especially if they have rail service and/or are included on package bus tours. You'll need to prepare yourself for that. And if you hit a wine area during the harvest... I did a short day-trip to Selestat (Alsace) and found it attractive but not touristy, so that's an exception. All the tourists were in Riquewihr, Ribeauville, Kaysersberg, etc. Colmar is a hotbed of tourists but is super beautiful, and I was glad I stayed there.

It's important to select a base city or town with good transportation links to the surrounding spots you want to visit. Be aware that a lot of the cute little towns you've heard of in Provence are extremely difficult if not impossible to reach by public transporatation, expecially outside the July-August period. The Riviera has much better transportation. Rick warns about this in his guide books.

Despite the title of your post, and its "or," you say you want to spend some time in Alsace and Switzerland. You do not have time for both, really, though I think that Burgundy or even Lyon would be within reach because the rail connections are so very good.

Since you have been to Switzerland and Alsace before, I am going to gently pitch Provence to you. It is a part of France with an ancient Mediterranean culture and history. The Roman antiquities are magnificent, and the countryside is beautiful. Early September would be an ideal time to visit. If you go, I'd recommend renting a car for that part of your visit. The rail connections to Paris are excellent.

Whether you go on to Nice is up to you, but if you have not purchased air tickets yet you could fly home from there and avoid a travel day, which is worth something.

In short I really think these are two separate options, north or south, and the closest you can come to splitting the difference would be to include Lyon in the northern run. But even that might be a destination too much. So, choose what calls to you.

You could take the train to Avignon or Aix and then rent a car for a two days to tour the Louberon/villages and nearby places like Arles and Nimes/Pont du Gard. You could also then take the train to Nice, Antibes or Villefranche-sur-mer and use that as a base to explore the Riviera coast via trains and bus (like Eze and Menton). The weather in early September will be still very warm and the water at 72 degrees or warmer. You can take a low cost flight back to Paris to rejoin your return flight. That is France's second most trafficked airport, because of the popularity of the region for visitors.

Another option is Lyon, with a tremendous food scene, with side trips possibly to Geneva and onward to Chamonix/Mt. Blanc. (You could even head into lower Bourgogne, if wine is your thing).

Dijon and Beaune/Bourgogne are an entirely separate diversions, I feel. Beautiful villages and countryside, and perfectly fine in September. (I lived over the Jura in Switzerland)

I really do love Alsace and the wine road villages, but if you have been there before and it's your friend's first time in Europe, it may feel a bit limiting. Basel is a nice town but maybe on the next tier of destinations.

I would train to Avignon or Arles and use as a base to visit towns in Provence like Nimes,Pont du Gard,Gordes,Les Baux,St Remy and Roussillon which should keep you busy.Lyon is a beautiful city with the Saone River splitting the old town hilly side from the Presqu'ile area which is bordered by the Rhone River.There are a lot of sights including Roman ruins in Lyon and a great food scene.We spent four nights in Lyon in May and would like to go back.
Mike

Thanks everyone for all these great options. We are supposed to leave next week, and hopefully we can get out of Houston. Hurricane Harvey created mayhem here. At this point after all this stress, just want to relax and enjoy life. Awesome suggestions.