San Diego is one of the southern California cities that I visit most often, as I have a good amount of family and friends that live down there. It's always sunny and beautiful in San Diego, so you can't go wrong visiting for a weekend getaway.
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If you're looking to stay on the beach and rent a house through Airbnb or VRBO, I recommend Mission Beach. I've stayed there with friends a few times on the stretch along the ocean front Boardwalk, which is always filled with people out and about, be it runners, bikers or walkers, there are always people exercising and taking in the amazing beach views. Look out for Slo-Mo, a full-time slow motion rollerblader who quit his day job as a doctor to live the easy life. He's a legend to locals and you can read more about him here.
Pacific Beach is a really young area, also on the beach and directly next to Mission Beach. You'll find lots of college students and 20-somethings hanging around this area. It is a bit more high energy than Mission beach, which has little bit more of a relaxed vibe. In PB, there are tons of restaurants and bars right on the beach and down the main stretch. It's a fun place to go out at night for drinks and dancing!