The largest indoor arena in the San Diego area is Pechanga, which only holds 14,600.
80 miles north, the Honda Center in Anaheim holds a max of 18.900. It's in a pretty good area, although most of the best hotels and restaurants are concentrated near Disneyland, which is 3 miles down the road.
The largest indoor arena in the LA area is probably the Crypto.com area (formerly the Staples Center), about 19,000. Downtown LA is pretty congested and would be difficult to get around.