As an SF local, what I enjoy most about my city is being able to walk around from neightborhood to neighborhood, enjoying the uniqueness of each. It always amazes me that visitors stick to the same well-travelled areas, most of which are completely ignored by locals, Fisherman's Wharf I'm looking in your direction.

Besides the excellent walking tour recommended earlier in this thread. Spend some time hitting some of the less touristed neighborhoods of the City. Just a sample if you want to go well off the beaten tourist path...

- The Mission is an amazing corner, great ethnic food, the murals, the people, the Mission itself, Dolores Park.
- Lower Haight neighborhood is as close as you will get to what Haight Ashbury once was.
- Cole Valley is my favorite neighborhood to just walk around in. Easy access to GG Park, Inner Sunset (see below) and the NEW NEW NEW DeYoung museum that open yesterday. http://www.thinker.org/deyoung/index.asp
- Inner Sunset - no tourists here, just locals
- Crissy Field - an amazing park at the foot of the GG Bridge.