The monsters shown in the movie are all references to original monsters in movies. Ginormica (Reese Witherspoon) is a reference to Attack of the 50 Foot Woman (1958), B.O.B. (Seth Rogen) is a reference to The Blob (1958), The Missing Link (Will Arnett) is a reference to Creature from the Black Lagoon (1954), and finally Dr. Cockroach, Ph.D (Hugh Laurie) is a reference to The Fly (1958).
For the scenes of Ginormica wandering the streets of San Francisco, a replica of the set was built, and Supervising Animator Line Korsgaard Andersen was videotaped walking around it as reference for the animators.
When the government agents arrive at the church to investigate the crash site, when the camera pans to the back of their van, when the door closes, you can see a camera crew visible in the reflection of the door.
The film has a localized version in Australia, where the News Reporter is not voiced by Ed Helms, but instead voiced by David Koch, a co-presenter of the morning show "Sunrise", seen on Channel 7 across Australia.
When Gallaxahr is talking to earth about what he is about to do, in the scene when Gallaxhar is talking in Times Square, New York City, on the top right corner, a scene from Madagascar (2005) can be seen of Marty talking to Alex.
The famous sound effect, the "Wilhelm Scream", is featured in this film. The scream was originally done in the 1950s by Sheb Wooley, who sung Flying Purple People Eater (1958), which was used in the closing credits.
After Susan saves B.O.B., Link, and Dr. Cockroach from being crushed on Gallaxhar's ship, after becoming Ginormica again, Dr. Cockroach says "By Hawking's chair." This is a reference to Stephen Hawking, a renowned academic, who is bound to a motorized wheelchair, due to amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, or A.L.S.
Early in the movie, B.O.B is bouncing a ball off the wall of his cell. This could be a reference to Hilts, the Cooler King (Steve McQueen) from The Great Escape (1963). McQueen played Steve Andrews in The Blob (1958) (B.O.B is a parody of the Blob).
The large aircraft used to transport the monsters to San Francisco is based on an actual Guppy aircraft. The first Guppy was built in 1962 for NASA by Aero Spacelines of California to transport spacecraft components.
The multi-colored pads that Dr. Cockroach dances on use the same sound effects as the light-up memorization game "Simon". The dancing in sync with the lighted pads is a reference to the arcade game Dance Dance Revolution (1998), in which you do the same thing, only in sync with the on-screen prompts.
The San Francisco streetcar that Dr. Cockroach modifies with rocket engines, is an Italian-made vintage Peter Witt streetcar in the 1928 white-and-yellow color scheme. The streetcar in the movie has number #2930 (as of release, not an assigned number).
The city of Modesto, California, is depicted as a small, rural farm town in this film, when in reality, it is a bustling city, complete with a shopping mall right off the California 99 freeway, that flows through the city.
When the Monsters are fighting the alien spacecraft on the Golden Gate bridge, it shows a solid middle divider between north and south lanes. The bridge actually uses yellow removable pylons, so the amount of lanes on a given side can be adjusted for commute hours.
'Renee Zellwegger''s 3rd Dreamworks Animation film, after Shark Tale (2004) and Bee Movie (2007). All those times had her voicing a Love Interest, but instead of being one to the Main Character, she voices the lady of the couple that first encounter Galaxhar's Giant Robot once it arrives on Earth.
The trivia items below may give away important plot points.
In the scene during the closing credits, the President asks the audience if anyone wants to freeze his head. Stephen Colbert, who provided the voice of the President, gives detailed outlines on how to unfreeze his head in an apocalyptic future in his book, "I Am America and So Can You".