Do not drive, if you can avoid it. Parking is a nightmare. Public transit is excellent. Wear comfy shoes as San Francisco is very hilly for walking! Go to Alcatraz where you get off on the island and are allowed to walk around - I thought that was pretty interesting. Go to North Beach for great Italian food.
Lombard Street (the crookedest street in the world) has some beautiful houses. The shopping on Market Street is pretty good.
If you like drag shows, go see Beach Blanket Babylon!
It's supposed to be a very impressive show.
http://www.beachblanketbabylon.com/
For a bit further afield:
Take BART and visit Berkeley....or
Take the Cal Train to Palo Alto and see Stanford (there is a shuttle from the Cal Train station to Stanford).
Also, in SF, the weather can change on a dime, so always make sure you have a light sweater with....umbrella is good too.
If you want to avoid sounding like a tourist, don't refer to San Francisco as "San Fran" nor "Frisco". It's either "San Francisco" or "The City". This was all carefully explained to me by my friend who lives in Russian Hill.