Even before the festival's opening, crowds waited in line for access badges Wednesday afternoon. The event, which is set to run for four days, is expected to attract more than 130,000 guests and host hundreds of exhibitors.
"The people who go through those doors, most of them are film fans and fans of pop culture, be it video games or movies or television shows, T-shirts or comic books, it's all part of this big cultural stew," says filmmaker Jon Favreau, who is set to premiere his latest movie, "Cowboys & Aliens," at Comic-Con. "These are people who normally interact with one another through the Internet. Then when you finally open it up to meeting in person, it just concentrates that experience."
Hollywood continues to command a headlining presence at Comic-Con, and Tinseltown offerings are some of the most anticipated at the festival.
"Captain America" will play in San Diego for a full day before its nationwide opening Friday, and star Chris Evans is set to introduce the earliest screening. "Cowboys & Aliens" will hold its world premiere at Comic-Con on Saturday - a festival first. Steven Spielberg is coming to the convention to talk about "The Adventures of Tin-Tin"; Sony is offering a peek at "The Amazing Spider-Man"; and the "Twilight" trio - Kristen Stewart, Taylor Lautner and Robert Pattinson - will again greet their fans at the Con.
As for the smaller screen, "True Blood," "Game of Thrones" and "The Walking Dead" are big draws, while new shows such as "Person of Interest," "Grimm" and "Terra Nova" will present preview footage and introduce their casts in an aim to attract viewers before their fall premieres.
New video games are also expected to score big at Comic-Con, where players can get an early look at sci-fi shooters "Halo" and "Gears of War 3" and the latest "Batman" and "Spider-Man" games.
The Associated Press contributed to this story.