I'm thinking about flying in to Vegas then driving to San Francisco or visa-a-versa. Is there an additional charge for different drop off? (one week rental)

Request a quote for same rental duration with different return location ( like pickup SF/return SF and pickup SF and return LV). You will know additional charge if any from these quotes. Most likely there would be an additional fee.

Yes if you drop off at a different location you have to pay a fee.