I don't know about the driving vs. taking the train aspect, but as to tips, several months ago I drove Marseilles to Nice as part of a 3000+ km driving trip (Paris to Carcassonne to Avignon to Apt to Marseilles to Nice to Monaco to Genoa to Lyon to Paris) and here are some thoughts:
1. Pay attention to speed limits and the speed cameras (you can find their locations on-line); my husband didn't and received a ticket in the mail several weeks after he returned.
2. Have cash for tolls just in case. For some tolls, my sister's French credit card did not work, my Chase BA card with a chip did not work, and my non-chip US cards did not work. For some reason, there were tolls where the only card that worked was a BA card without a chip. After messing around with various cards, we just used cash... a lot of cash; tolls are expensive. There is a website (I believe it is a michelin based one) that is handy for calculating tolls and gas cost.
3. Rental Car companies: We have rented from Hertz, Sixt and Auto Europe for cars in France. I am always struck by how expensive they are unless you can get by with a small car. The prices can be hugely different from each other and a lot depends on whether you are returning the car to the same location (it sounds like you are not) and the size of the car. For this trip, I found a great price at Hertz (using either the Amex Plat or the AAA discount; I don't recall) for a 5-seater mini-wagon (manual trans.) that I rented in and returned to Paris. We also needed a very large car (8 seater plus luggage) that my husband could pick up in Paris and drop at the train station in Avignon. We used Auto Europe for my husband's car; it was the only place I could find a big enough car and it had no drop off fee (which, if I recall, was hundreds of dollars with Hertz). Be careful with Auto Europe though; there was an additional couple of hundred Euro charged to us at the end ("disclosed", but somewhat misleading). We also rented a defective car from them once. I spent a fair amount of time re-checking rental cars and saved a lot by re-booking when a lower price appeared.
4. Between Nice and Marseilles, you could look into Antibes. Don't know when you are going, but traffic can be bad on the route that takes you along the water. Marseilles is a PITA to drive around, but there were places that were easier to see by car.