*ahem*
1). Bring your own food. Conventions (and especially Comic Con) take advantage of the massive attendance to sell expensive eats. Even if you get food outside, it's still Downtown San Diego, and unless you're planning to walk really far (or if you have transportation), you're gonna pay a lot for food.
2). Make use of any public transportation you can find. San Diego has a (limited) railway system, but it has a special line (the red line, I believe) for special events like this. Parking at one of the major railway stops and purchasing a trolley ticket will ultimately save you time and money as a). you don't have to pay for parking and b). even if you can afford the [horrendously expensive] conv.cen. parking, good luck trying to find a spot.
3). If you are local, just let someone drop you off and pick you up.
4). PLAN. Comic con is bigger and more diverse than any niche convetion (sci-fi, anime, roleplaying, fantasy,
furry), so it's easy to get overwhelmed. Find a schedule of events ahead of time and pick what events/panels/whatever because...
5). You will be waiting in a line. A LOT. Some of the really 'hot' events like panels for upcoming blockbusters have gigantic lines that fill up hours before the line actually begins. And picking up your badge is no trivial thing either.
6). If you and a friend are NOT planning to attend the con all four days, get a four-day badge anyway and split the days between the two of. Out of courtesy, split the cost.
7). Cultivate the fruits of the Spirit. You know, love, joy, peace, patience, kindness etc. etc. There will be a lot of impatient, unkind, and rude idiots in the convention center so you want to combat that.