Aix, Arles or Avignon between Lyon & Marseille

If you drive down through Grenoble, I would stop in Sisteron (lovely town), but then you miss all the ruins.So I think you shouldn't drive through Grenoble, drive straight south from Lyon instead. Grenoble isn't worth the detour.

As for places to stay, since you have a car, you have freedom to stay in a smaller town: Uzès, St Rémy, Isle-sur-la Sorgue would fit the bill nicely (in that order) given your priorities. Uzès has a delightful market on Saturdays.

If for some reason you prefer a larger town, then Arles is my favorite (big market day is also Saturday). I love Aix too, but it's very close to Marseille and quite far from the Roman sites. Avignon has a more 'workaday' feel, being the regional hub it's convenient for those who don't have a car.

I agree with this advice, though have not been to Sisteron or Uzes. Have been to all the other places.

Uzès, St Rémy, Isle-sur-la Sorgue would fit the bill nicely

I've been to all 3, and would agree with those choices, as well as the other they're in.

Of the three you mention, Arles would be my favorite by far. In spite of stumbling into Arles on a huge festival day which made navigation and parking crazy, we still really loved it:
https://janettravels.wordpress.com/2016/11/20/quick-stop-in-arles/

If you have a car I think which city you stay in between Avignon and Arles really doesn't matter. Avignon usually gets the nod because of public transportation access but with a car the distances are pretty close. Arles is not a car friendly town in the interior so park outside the city walls or stay on the ring road. I think Aix is too far from the generally recommended "ruins" sights.
Arles gets my vote as a town to stay in over Avignon but you could stop in Aix on the way to Marseille to see it.
Market days vary by town so when you know what days of the week you'll be there you can plan accordingly.

Ruins:
-Vaison la Romane; charming small town with Roman and medieval layers and ruined castle that you can't tour. Market day is Tuesday. It's in an area that lends itself to biking and hiking as well.
-Orange; The Theater is basically Orange's only big ruin but it's amazing. I was not prepared for the scale of it and I highly recommend making the time to stop there.
-Pont du Gard is easy by car from either Avignon or Arles but is slightly closer to Avignon. There are a lot of weaving nature trails around the large park site. Take you hiking shoes and plan on several hours of wandering. Chances are you'll stumble across sections of aqueduct along the way. There are also river adventures under the bridge that might interest you.
-Gallum at St. Remy is a remarkable site and the town is small upscale, charming Provincial town.
-Les Baux has a big ruined castle on the hill very close to St Remy and close to Arles.
-Alres has the colosseum and the theater site and a good little museum and many little restaurants.

I wrote up my recent ruins tour of Lyon and Provence here:
https://community.ricksteves.com/travel-forum/trip-reports/lyon-and-vaison-la-romaine-ancient-ruins-tour-1-2
https://community.ricksteves.com/travel-forum/trip-reports/avignon-pont-du-gard-orange-st-remy-arles-ancient-ruins-tour-2-2

Also Lyon has some decent outdoor activities and it is a very fit running and biking town so check on outdoor activities even though it is a city. And obviously don't miss the Roman theaters and very good museum in Lyon.

I'm jealous - have a great trip!
=Tod

To all, thank you for the advice so far, and Tod, I will read your review! We're fine with driving to a neighboring town, parking in an outer ring lot and walking or taking public transportation in to town. I'm learning that I like the small towns and gems you find when you can get off the beaten path.

On a side note, we parked a car in Leuven Belgium, and thought that the sign indicated it would be okay to leave the car there for 2 days. On the morning of our departure, we walked the ~1 mile from our hotel, and the car was GONE! We walked back to the hotel, got help in calling the police station, where they told us that we would have come in to report the car as stolen. We started walking that way, but decided to walk back by the parking lot again. Lo and behold, the car had been moved to another spot about 30 yards away. We never thought to look around the lot. The exterior row we had parked in apparently was supposed to be vacated on Friday nights for the charter buses to take the university students home or on trips.

My daughter was living in Grenoble and we found it to be a great place to visit. The old town the bubbles and chartreuse massif were wonderful. No tourists. We drove to Sisteron thru a beautifully scenic mountain area. Sisteron was dramatic walked around town went to the citadel, cemetery. Stayed at citadel hotel. And drove to near baux for the next night. Have fun

Defintely not Aix. We didn't like Aix at all. It's not a small town. Big city and lots of traffic.

My wife and I had exactly the same dilemma, and chose Aix as the base and ended up seeing Arles and Avignon for day trips by car. I think the choice of city depends on your personal preferences. Of the three, Aix is the most posh and wealthy, which is both good and bad. On the plus side, it is the most well-preserved and pretty, as compared to Arles which was more run down and Avignon which I found somewhat gritty. Aix also has an excellent market. On the downside, my wife and I fond the people in Aix somewhat snobby and "Parisian" in their attitude if that makes sense. On the balance, we were still happy with our choice.