Hi italdesign - It really depends on your age, interests and time available. What is kind of wonderful about living here (I've been here 20 years) is that there is literally something for everyone, from a gay standpoint. The Castro is a good historical reference point and worth a walkthrough, but the exciting and interesting areas of the city these days (in my view) are now Hayes Valley and The Embarcadero. Absolute musts for a first time visitor in my mind are:

1. Golden Gate Bridge
2. The new Ferry Building and a walk along the bay looking toward the Bay Bridge
3. Ride a cable car
4. Alcatraz (book early - tickets are sold out months in advance)
5. Castro crawl on a weekend night
6. A really nice dinner at any of our hundreds of exceptional eateries (SF is one of the world's great food cities)
7. The view from Twin Peaks on a clear day
8. Union Square for people watching and lounging outdoors with coffee and a paper
9. The Transamerica Pyramid, new Museum of Modern Art, and our gorgeous Beaux Arts city hall are among our more interesting buildings

Have a great visit.