Cow Hollow along Union Street is a great, untouristed neighborhood with excellent restaurants (see my Dining entry) and shops. For a glimpse of San Fran's Beat history, go to Lawrence Ferlinghetti's City Lights bookstore in North Beach. Lawrence still mans the counter, and the selection is great. You'll also find photos and posters of Lawrence with Ginsberg, Kerouac, and others from the era. North Beach is also a good neighborhood for wandering (once you get into the hills) - if you walk to the Coit Tower, you'll pass some beautiful homes.
Quick Tips:
Fisherman's Wharf is a tourist trap. I wouldn't recommend going at all, except to catch the ferry to Alcatraz, Angel Island, or Sausalito/Tiburon. Make sure you book your Alcatraz visit well in advance; when I was there, they were sold out for a week. Do visit San Francisco's Museum of Modern Art, which holds an excellent permanent collection and hosts world-class traveling exhibits. If you love baseball, go to Pac Bell Park. It's a fantastic place to watch a game. As for the Golden Gate Bridge... There is absolutely nothing else like it. Pictures do not do it justice. Go see it. There are parks on both sides, and you can walk along the bridge from one side to the other.
Best Way To Get Around:
The cable cars can get extremely crowded, and the area they serve is limited. Taxis are common and convenient. If you have a car, you'll find that parking is a problem; it really isn't necessary to have one in such a compact city, but you'll definitely need it to visit Napa, Santa Cruz, and the other areas. Use the ferry to visit Sausalito or Tiburon.