The Hotel Hyatt Regency Mission Bay (aka Hyatt Regency Islandia) is very close (ca a 10 min drive)from the airport and downtown, and minutes to Sea World (so if you have kids..). The views from the 'Ocean View' rooms are extraordinary. We took this from ours (an upgrade from a standard room) last year when we visited for our first wedding anniversary.
I would recommend you go during a special occasion, because you might be able to negotiate upgrades on those grounds. Unless of course you're naturally smooth and can charm the pants off of anyone. We also managed to get free parking, which was great, considering it's about $16 daily.
We did not try the main meals at the in-house restaurant (Blue Bay California Bistro), but they served up some seriously tasty light night munchies! A nice hotel where the decor is not extraordinary, but its settings, views, and locations are.