I normally paddle Mission Bay 1-2 times per week for the past year to 18 months. This is one of my favorite spots in San Diego, and I am never disappointed in any of my trips.
There are many places to launch, my two favorite being Bahia Point if I provide my own boat, or Aqua Adventures if you need to rent a boat. That being said, Jen and Aqua Adventures provide an excellent assortment of rental boats, from sit on tops to plastic and fiberglass sit-ins from a variety of manufactures.
As for the bay, I would recommend early morning or evening paddles on the weekends, especially during the summer. The bay can get very crowded with tourist during peak summer months, June till early September. Unfortunately, outfitters will rent Jet Skis and speed boats to anyone with money so it can get very dangerous in peak season so beware of crazies!!!
I often like to take my boat out around 5 to 6PM during the week for a good 5-7 mile paddle. The water is great, and there are plenty of places to paddle...so you can add variety to your trips. During the summer you can land at the Catamaran Resort and take in a real cool Polynesian Dance show and grab a drink. I will say that the water is not always the cleanest, and during the summer there seems to be a fair amount of trash etc that finds its way into the bay. Evening paddles during off season is like paddling on glass!!!
On clear nights you get awesome views of the city and Sea World. During the summer you can catch Sea World Fireworks daily at 9:50PM, and on the weekends the rest of the year at 8:50PM. After your paddle, head over to Mission Beach and check out the local watering holes and restaurants. Also check out Rockys in Crown Point for a great burger and beer after a paddle. If you are in San Diego and looking for a beautiful paddle, you wont be disappointed.
Take I-8 West to Mission Bay, or Sea World Drive from I-5...follow signs
Many locations to launch
Also see this excerpt on Mission Bay from the book "Adventure Kayaking - Trips from Big Sur to San Diego" by Robert Mohle