Easiest Train station in Paris to Rent a Car?

There are Sixt, Enterprise, Avis, and Europecar locations at La Defense station of the RER A and No 1 Metro. It is heading out of town in the direction of Normandy.

Edit - Per your other post, there are also Sixt, Avis, and Europecar locations by the TGV station in Chambery.

It's not on the way, but ORLY airport has a big supply of cars and easy access to main roads,

I like Sam's suggestion of La Defense - it's in the direction of Normandy and reasonably close to the motorway without much city driving required.

One quick warning about La Defense - a normal central zone Paris city transport ticket will only take you there by the Metro Line 1 - if you use the RER Line A you need to get a specific ticket and may get fined if you try to use a normal one. That seems to catch a lot of people out.

A quick check of the map suggests that departing Paris from somewhere in the southwest corner would give easy access to A13 and a direct shot to Normandy.

I was just wondering this same thing, but we will be heading towards Reims. Perhaps I should be checking for rental agencies
near Gare de l'Est? Or better yet...maybe just take the train to Reims and then, after our short stay, rent a care in Reims?

That direction, CDG would work, unless there is some kind of expensive adder for renting there. There is also a Hertz at Marne La Vallee Chessy station of the RER A. That's Disneyland. The A-4 to Reims is just south of Disneyland.

For the person going to Reims from Paris, I would say take the train and rent the car when you get to Nimes unless you absolutely need automatic transmission.
For the person going to Normandy, I would pick up the car either from La Defense as suggested above or rent from Europcar and pick up from the location on Avenue Foch.