San Francisco is an underused setting in games. I still need to play Driver: San Francisco, but I'm not sure how much it takes advantage of the city.
Daedalic's new adventure game 1954: San Francisco seems to, as you split playtime between Christine, scouring the streets of San Francisco, and her husband, Joe, whose doing a 40 year stint on The Rock.
Meanwhile, there's a large cash sum at stake in this seedy noir. As Joe, you'll have to pull a Clint Eastwood and escape from Alcatraz. As Christine, you can abet your husband's escape or leave him to rot in jail and go shack up with his ex-partner. Damn.