San Francisco is my favorite city to visit and do so once every 2 years, usually to catch a Warriors game. We stay around the Union Square area and take Muni (bus, light rail) everywhere. The city appears to be as clean and safe as before, however, many restaurants/businesses have closed down or are open fewer hours. First timer activities should include taking a cable car trip to Pier 39 area, visiting Alcatraz (purchase tickets in advance), catching the museums in Golden Gate Park. As already mentioned, rent a bike at Pier 39, and ride to Sausalito via the Golden Gate Bridge for lunch before taking the ferry back to where you began.
Great and unique neighborhoods for drinks and food include Castro, Mission, Pacific Heights, and my two favorites, Chinatown and North Beach. Great Chinese food at Hong Kong Clay Pot in Chinatown, and amazing Italian food in North Beach, including Golden Boy Pizza and Soto Mare for seafood. Plenty of hole in the wall bars all over town, and great food in every neighborhood. Grab a drink in the Tonga Room in the Fairmont, and a cocktail in the Top of the Mark across the street at the InterContinental for more of an upscale experience.
If you can't make it to Alcatraz, take a boat tour of the bay that will include getting you close to Alcatraz, and will take you under the Golden Gate Bridge for a unique view of that structure. Spend time around Pier 39 (Fisherman's Warf) too. It's touristy but a lot of sights to see, and its especially kid friendly. Catch a Giant's game at Oracle Park, but don't forget your cold weather gear if it's at night!
There's no denying San Francisco is not the same city it was 5 years ago, but I've never felt unsafe anywhere, including being on public transportation at night. However, avoid the Tenderloin area and mid-Market Street and you be fine. You will see homeless, but nothing that you won't see in any other major city, and I have yet to see shit on the street. Can't wait for my trip in October. Enjoy yours next month!