Suggestions - Drive or Train from Nice to Avignon

Here are a few comments on the train travel you are considering. That overnight train is listed as taking more than 12 hours, not my idea of fun even though I like trains. During daylight the trip takes less than half that time. An airliner will take 90 minutes. Yes, planes require more time at each end to reach airports, check in, and so on, but if purchased well in advance the price competes with the train.
However, if you are flying trans-Atlantic to Paris and then intending to continue travel the same day, it will probably be more efficient to use a multi-destination search to connect through Paris to Nice or Marseille as part of the same ticket. Use the train or car for the southern region. Return to Paris by surface transport for a flight home from there, or connect from the Marseille airport.
By the way, while the train from Nice to Avignon is a TGV, it does not move at high speed on that section of the route. You will see some of the southern coast from that train but also some of the not-so-scenic industrial suburbs.

I agree with flying into Nice or Marseille and out from Paris, if those tickets are not yet locked into roundtrip Paris. I recommend driving from Nice through the Luberon with a night or two in that region, as I did last year. That's nice, rural, scenic driving and going to Avignon first feels like unnecessary backtracking. You can drop the car in Avignon, then train from there to Paris.

Thanks for the suggestions. The flights in & out of Paris are unfortunately already booked. Based on what I have read seems like Avignon itself is less of an attraction - it could be a base for exploring that region but spending time in the Luberon could be more interesting.

Since you're not overly enamored with the possibilities in Avignon, and I agree with that, then a smaller town can make just as good a home base. Parking in Avignon is an added expense.