Jaime's Guide to Touring San Francisco
SF is 7 miles across by 7 miles high, and most of the interesting stuff is in the northern (top) half. It's at the tip of a peninsula and surrounded on three sides by water, which can confuse visitors-- just seeing water in the distance does not help you orient yourself! A great thing to do early in your trip is to drive, take a bus, or walk, to the top of Twin Peaks, where you'll be able to see the entire city-- the ocean, Golden Gate, north and south Bays, and the east bay cities. This will give you an excellent orientation (bring your map with you to identify sites you'll visit later).
THINGS TO SEE
Note: it might be a better use of your time to experience things and people rather than just passively see "stuff". SF has plenty of traditional tourist stuff, but other than telling your friends, "yes, I saw Fisherman's Wharf", it is probably more interesting to have seen something.
PEOPLE/CULTURE TO EXPERIENCE
See a drag show. San Francisco is a city of self-expression. Seek out local drag, local bands, local artists (including the Murals of The Mission district).
Bicycle, either up to and across the Golden Gate Bridge, or as a way to get around town, especially when visiting Golden Gate Park.
Hike into the residential hills. The nice houses are on tops of hills. Climb some stairs that are installed in place of streets where the street would be too steep.
WHAT NOT TO DO
Fisherman's Wharf is a total tourist trap, there's virtually nothing authentic there; mostly t-shirt and trinket shops and bad motels. However, the seals who bask in the sun 20 feet from the shopping-mall pier are a sight to see.
There are many ugly parts of the city, that, while realistic, should be avoided unless you want to see the gritty and down-and-out side of the people. This includes the "mid-market" area- Market street between 6th St and Valencia St; The Tenderloin neighborhood (adjacent to that area), the southwestern part of South Of Market (south of that area).
Bicycle. Since SF is so compact, bicycles are among the best way to get around quickly. Plus you'll see a lot of stuff en route, which you'd miss in a subway or bus. Be sure to lock your bike including both wheels securely every time you park. The big disadvantage of rental bikes is getting them and returning them; there are many tourist rental shops, but some are expensive. Some of the less-well-known and cheaper include the Backpackers Center (http://sfbackpackers.com/), and The Bike Hut. Sports Basement's Presidio store is the place to rent a high-performance real road bike if you want to do serious bicycling.
Get a Clipper Card. This is SF's answer to London's Oyster or Hong Kong's Octopus-- an electronic fare-payment card that works on all the transit systems. Load "cash value" onto your card (one card per person) and you can then conveniently travel on MUNI bus, MUNI trolley/light-rail, BART subway, Ferries, and Cable Cars. Bus and subway fare is $2 within the city; Cable Cars are $6.
Walking is of course the best way to really experience the city, but it can take ~2 hours to traverse the entire city. So it's a good choice if you have time to spare and don't want to be rushed. You also get the option of taking a bus or trolley if you get tired.