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San Francisco Advice for September 2014 trip

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My best friend and I (both 53) are planning a long weekend in San Francisco as a girls weekend. In the past we have stayed in a Union Square area hotel but this time would like to stay in a neighborhood and probably do a vacation rental for 4-5 days. We will want to shop but we will also want to just chat and eat local, walk etc. Need recommendations on a safe, good neighborhood area with good transit connections to SFO and other areas of town plus any hints on a good vacation rental source. Thanks!

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