If price is not an issue, stay in the Presidio/GGNRA and take cabs. The Hotel Tomo in Japantown is quite interesting. There are a number of small, eccentric, high-end boutique hotels in Pacific Heights. Move around interesting areas of the city. If the weather is good, go to Half Moon Bay for a day or two. If you stay in SOMA/the CBD/Union Square/Fin Dist you will be guaranteed to meet many more native Midwesterners than native Californians. Tourists are great, but San Francisco residents are by far more interesting.