Car rental-Lyon

Should be car rental locations at Part Dieu, but certainly at the airport. Advantage of the airport is that it is outside of Lyon so city traffic is not an issue and it is on the side of Lyon closer to the Alps. Disadvantage could be higher cost due to it being an airport location, but it will be open all hours. City locations often close 2 hours for lunch in the middle of the day and not open Sundays.

I would do what Sam suggests: take train to Lyon Saint Exupéry (instead of Lyon Part Dieu) and rent a car at the airport. I do not think it will be more expensive.
At the airport, the car rental offices are reached by shuttle bus or a 15-min walk. The bus is better. You'll have to first head to the airport terminal from the adjacent train station, then take the bus in front of the terminal. Signage is OK. It sounds like a hassle, but it is less of a hassle than driving out of Lyon from Part Dieu station.

Agree that it would be much easier to deal with rental at St Exupéry than at Part Dieu. My husband and I have rented cars at both locations multiple times. Getting away from Part Dieu is super confusing, even for us knowing the city really well and using Google Maps. The new rental garage at Part Dieu is a big improvement on the old set-up, but there is a lot of construction in the area due to the renovation of the train station. From St Exupéry it's pretty much like at a US airport - a shuttle to the cars, then you exit the airport onto a highway. You can be on your way east to the Alps quite quickly.

With a similar situtation - I settled on renting from Sixt - Lyon Cours Franklin Roosevelt. Based on my Google Maps research combined with my daughter's on-the-Lyon-ground reports, it seems pretty easy to get there from Viex Lyon, it's open early (8am), is a bit less expensive then renting from a major transport hub, and seems like an easy-enough drive back to pick up the luggage and head out of town. Good luck with whatever you decide. Sounds like a fun route.

Not sure which train station is best but we are renting a car in Lyon for 6 days in, picking it up at 8 Avenue George Pompidou Lyon TGV station and dropping it off in Reims. We are getting it from Enterprise at a great price thru Expedia and had also tried with Costoco. At this station there are the Enterprise/National/Alamo desk is located inside the TGV station. Unfortunately for us we are there over July 14 and had to rent it one day early, storing it in a parking lot kind of close to the hotel. You might email your hotel and ask which is the easier train station to leave the city.