The Castro

The Castro District, known otherwise as simply, "the Castro," is widely considered the United States' gay capital. Not only is it the largest, but also the country's first.
Regardless of a visitor's sexual orientation, the Castro is full of wonderful attractions, including the Castro Theatre, one of San Francisco's more popular movie palaces, complete with a world-class interior chandelier and designed with a colonial Spanish Baroque facade. 
Perhaps the area's most culturally significant landmark, the GLBT Historical Society includes a museum and archives documenting the history of the gay and lesbian communities in the U.S. Aside from its core purpose, the building also houses other interesting institutions including the Cartoon Art Museum, which features well over 6,000 different cartoons and comics, and the Catharine Clark Gallery, an exhibition including  different forms of media for contemporary, living artists.
Also be sure to check out Harvey Milk Plaza, named after the famous openly gay politician, commonly labeled the "martyr of gay rights."

Practical Info

The most efficient way to commute to the Castro District is via the MUNI Metro system, either by the L, K, or M line. For a more scenic and exciting experience you can also take the famous F Market streetcar line that will tour you through the Castro's lovely downtown area and Fisherman's Wharf.