Driving to Napa is an hour from SF if you're staying in fisherman's wharf or Lombard / Marina area. It's even more time from SFO. I personally don't think it's worth driving to Napa if you only have 2 full days in SF because I think there's a ton to see and enjoy in SF.
My suggestion:
Stay at a hotel in north part of SF.
Thursday - arrival; Bart / taxi / lyft to hotel
Friday - Alcatraz, sightseeing, etc
Saturday - fetch rental in SF, go to Napa, park car in hotel lot
Sunday - return rental in SFO and onward to next destination
Note - don't drink too much when driving or it could really ruin your vacation.