What is the best train strategy for making this trip?
Would you recommend driving as an alternative? Renting a car in Venice and driving to Avignon? (Our trip also calls for driving from Avignon to Carcassonne, Nantes/Loire, and in to Orleans where we will turn in the car and take the train in to Paris.
There is a stiff fee for renting a car in one country and dropping it off in another. If you want to have a car to tour small towns in Tuscany, then you might save money by dropping the car in Genova, taking a train to Nice, and picking up another car there.
The link Steve gave you has expired. Go here for the English version of the DB (German Rail) site. After you get summary timetables for Milano-Avignon, click on the arrow to the left of each departure time to see the connecting points. You can also click on "Show map."
The DB site shows a Milano-Chambery-Lyon-Avignon early morning route through the mountains that looks good to me.