We stayed in Pacific Beach. Lots of night life there. We loved it!
I lived in Little Italy for a about a year and a half, it's close enough to downtown to walk but you aren't gonna hear the bars let out at 2am, plenty of good spots there too, the Princess Pub was my second home.
Just make sure to get a burger at hodads
North Park or South Park. North Park is busting at the seams with breweries and they are the gayborhood of SD so you know they have all the good food too! They do lack immediate proximity to the beach, but a short drive will get you there.
Depends on what you want to do. We like to stay by the ocean so we stay near Mission Beach but it’s not as convenient for going out purposes. I do recommend Hash House a Go Go for a fun breakfast experience. Just go early or the lines are insane.
Mission beach gets my vote.
Definitely NOT Gaslamp, unless you're looking for touristy things. Kirps is right about Little Italy, stop by the farmers market.
Anywhere around Balboa Park, specifically North Park is fucking awesome for great beer and food. Modern Times Beer, Fall Brewing Company, North Park Beer Co.. City Tacos, The Mission / North Park, Bahn Thai Restaurant, San Diego Chicken Pie Shop, the list goes on.
Head north to the beautiful beaches (Del Mar) or to Coronado. Head south for some amazing tacos.. Tacos El Gordo • H Street.
Ocean Beach if you want calmer laid back old town on the beach. Pacific Beach if you want to be closer to the action and boardwalk. Anywhere near Mission Bay is good. Balboa Park is also really nice, it's not right on the beach but you've got the San Diego Zoo and museums, cultural exhibits, gardens and such. I used to stay on a yacht in the marina at Bahia resort every weekend. They have a lot of weddings there, it's a nice place and just a couple blocks from the boardwalk/beach. It's in Pacific Beach (PB) right on Mission Bay. I'd actually recommend that area.
Michael C. Brook
I also lived in Little Italy for about 18 months, and can definitely vouch for the number of great restaurants, good vibe, and proximity to downtown. Gaslamp is fine to visit, but I wouldn't stay there. I was just in Little Italy again last week and there's all kinds of new places that have popped up in the last 2 years. If you want more beach life, there's a cool modern hotel called Tower 23 in Pacific Beach that I've stayed at a couple times; right on the boardwalk. If you want the ocean with less party atmosphere which PB can bring, I'd check out La Jolla. Had a friend that found an Air BnB there and loved it (eat breakfast at Cody's if you do). Happy to send you an email with more details of restaurants and things to check out if you're interested...