Both Stone Brewery locations are awesome. One is in Escondido and has this beautiful outdoor area with trees, chairs, benches, fire pits (or whatever), and a little water feature. The other is in Liberty Station, closer to the airport/Point Loma and has a huge flat patio with a bocce ball area, tables, chairs, and kind of a desert-y feel. They both have indoor space to eat and drink, as well as outdoor bars.
Ballast Point is great, that's in Little Italy. Great food, pretty laid back ambiance. Down the street from that you can stop by Bottlecraft which has beers you can buy and drink there or just take them home. I think they also have flights for specific beers. No food here but you're allowed to bring stuff in from what I've seen. They also have games here which is nice.
In South Park area there's Thorn S Brewery. They didn't have food last time I went there, but they had a great selection of beer and it was all really really good. Its a tiny little place, I think theres two rooms but I've only been in the front room.
Modern Times and Hess are in North Park (somewhat close to 30th and University). Both serve great beer and have a nice environment. A shop or two over from Modern Times is Underbelly, a delicious restaurant that serves a really interesting variety of things but I've only had their seafood salad which was amazing.
Mission Brewery is downtown and I think is inside the old Wonderbread factory? Its a brick building that has a lot of open space, tables, etc. You could do the tour as well, which was nice when I went. (Groupon!)
Green Flash is also kind of nice. From what I remember it was very warehouse-y but the beer was great as well as the service.
Karl Strauss I think has restaurants in both downtown and La Jolla. Good food. Nice feel. More restauranty from what I remember though.
If you go to Coronado, there's Coronado Brewing Co that has food and beer. I'm not such a fan of the food or ambiance, but it wasn't a bad experience at all.
For North County, in addition to Stone there's Mother Earth, which I've been to. Kind of industrial vibe, open, nice. I liked it a lot. Plus they had some dogs and children which was kind of interesting. There's Booze Brothers in Vista as well. Ive only been there once, I hate the name but love the beer, the people, the ambiance. Dog friendly. I remember there being couches and nice little hang out areas. There's also Lost Abbey and right next to that is another brewery but I cannot recall the name. I think these are Vista/San Marcos area if I remember correctly. Lost Abbey's tasting room is also warehouse-y, and laid back. I don't recall there being anywhere to sit down, but it was nice to stop by. Also, in Solana Beach/Encinitas there's Culture Brewing. Also not a lot of seating, but they let you get little 3oz tasters which was nice. Great beer.
Rock Bottom Brewery is also decent. It's in La Jolla area. I have only been once, for one beer, so I don't remember much.
A couple I haven't been to but have heard about are Monkey Paw in downtown, Saint Archer Brewing Co, and Societe Brewing Company in Clairemont. I have had all their beer though, and like them.
I think there's also a couple locations for Pizza Port. One in Ocean Beach, one in Encinitas or Oceanside, I don't remember. You can always find great, interesting beers there.
A couple places that have good beer selection are Slater's 50/50 (Liberty Station/Point Loma), Small Bar (Normal Heights ish), Sessions Public (border between Ocean Beach and Point Loma), Tiger Tiger in North Park area, and I've heard that Hamilton's has great selection as well.
That's all I can think of off the top of my head, so if you need more suggestions or are looking for something specific, don't hesitate to ask!