Tenderloin is triangular area between Market, Van Ness, and stops a couple blocks before Union Square (around HIlton). Some decent hotels are in the Tenderloin, but usually up near Sutter or Post. It's the "lower" Tenderloin (Market between 6th and Van Ness) that gets the seedy reputation. The "upper" part is fine.
Not so nice section of town is around 6th and 9th and Market, as there's some adult theaters and such there. However, it's easy enough to bypass that section of town by hopping onto the various Muni vehicles that travel on (or under) Market St. and pay the $1.25 fare (per person of course).
Should you need help, there's a police station right around 6th and Market (on Eddy actually) and another one around Hotel Renoir (8th and Market) usually with several squad cars around. Or just dial 911 on any public phone.
South of Market is extremely quiet at night except around specific night clubs and such. Definitely take a cab to your destination and a cab going back.
Consider joining one of those "party bus" tours on the weekends, or even hire a limo for pickup and drop-off (it's less expensive than you think though 15-20% tip is expected).
Civic Center (around city hall, 9th and Market) is tolerable, but you may see more homeless people than you're used to in a big city. However, they are generally harmless as long as you don't gawk.
In general, tourists are not bothered unless you're just plainly UNalert for dangers. Don't stray TOO far off the beaten path and you should have a great time in San Francisco.
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