From my experience, broadly speaking Saturdays are better than Sundays, where car rental locations are often indeed closed entirely.
However, these days I think you can generally find pretty reliable hours of operation information online for individual car-rental locations, particularly for locations of major car rental companies (Avis, Hertz, etc.) If you're in the trip planning stage it's worth taking a look at actual locations to see what the hours look like -- might as well look early so you don't plan an entire leg of a trip around picking up a car on a day when the branch is not open.