Hopping on the Muni Metro light rail opens up a lot of options on your SF layover. Muni light rail is safe and modern (at least in my experience), relatively efficient and gets you out of the downtown core to some nicer neighborhood places. If you hit the timing right with Muni, you can be to most of these places 15-25 minutes after you walk out of the hotel.
Put a Clipper transit card on your phone (easy to do, follow the link below) and you're good to go.
https://www.clippercard.com/ClipperWeb/pay-with-phone
From Powell Street station (5 minute walk from the hotel), hop on the N-JUDAH (dark blue) line OUTBOUND toward OCEAN BEACH. It runs underground for a while and then comes above ground at Duboce and Church.
Places along the Muni line that I've discovered over the years, arranged by stop/station:
Duboce & Noe Stop (4 stops, ~15 mins from hotel):
Duboce Park Cafe: Cozy little neighborhood corner place, good coffee and breakfast/lunch food. You can sit at a shady sidewalk table when the weather is nice. The cafe is adjacent to the dog-friendly Duboce Park which itself sits adjacent to a row of handsome Edwardian (Victorian?) houses.
If you walk across Duboce park and then continue a couple of blocks, you'll reach the Lower Haight (different than Upper Haight, which is the hippie Haight-Ashbury part). There are some good places on Haight between Steiner and Fillmore. Memphis Minnie's BBQ Joint for BBQ. Toronado has a huge selection of draft beers.
Carl and Cole Stop (4 stops, ~20 mins from hotel):
Cole Valley Tavern: Upscale neighborhood bar and grill in a bustling location. Excellent drinks and food. Menu skews toward well-made comfort food standards. Get a soft-serve cone from their take-out window.
Wooden Coffee House: Third-wave neighborhood coffee-and-laptops place. Decent selection of baked goods. Nice window seating area overlooking the sidewalk/street. There's sometimes a parrot there.
Say Cheese: killer sandwiches plus gourmet goodies and wine shop. Sidewalk benches in front to enjoy your food and people-watch.
Irving and 6th (5 stops, ~22 mins from hotel):
Lime Tree: Singaporean/Indonesian. Absolute hole in the wall, inexpensive, lots of UCSF students. Outstanding laksa and Singaporean curry noodles.
Yellow Submarine: Great toasted submarine sandwiches and homemade potato chips.
Irving and 9th (6 stops, ~25 mins from hotel):
About 1.5 blocks from Golden Gate Park. An easy walk to the DeYoung Museum, the Academy of Sciences, or the Botanical Gardens. Lots of good food options on 9th Ave. From the Irving and 9th Muni stop, walking toward the park there's:
Arizmendi Bakery. All the baked goods your heart could desire, plus pizza slices that change daily.
Art's Cafe: True neighborhood greasy-spoon diner. Narrow counter, vinyl stools bolted to the floor. Menu is everything you'd expect plus a bulgogi and bibimbap sub-menu.
Ebisu: Hole in the wall neighborhood sushi place. Great and reasonably priced (for San Francisco, at least).
Fiorella Sunset: New-ish neighborhood Italian restaurant. Great pizzas and pasta. Open-air rooftop patio seating on the second floor is great when it's a sunny day. Apparently they have a speakeasy in the restaurant called Bar Noninna.
Underdogs Tres: Mexican cantina/taqueria with bar and seasonal local sportsball on TV. Patio out back.
Tartine Inner Sunset: An offshoot of the original Tartine Bakery in the Mission. All-day dining. Great-quality food. Sandwiches are served on their rightfully famous homemade bread.
um.ma: Killer "fancy" Korean BBQ with a patio in the back.
So many more places to recommend but I'm going to stop now.
Enjoy your layovers!