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 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 Healms but instead voiced by David Koch, a co presenter of morning show "Sunrise" seen on Channel 7 throughout Australia.
The infamous sound effect, the "Wilhelm Scream: is featured in this film. The scream was originally done in the 1950s by Sheb Wooley, who sings "Flying Purple People Eater," (1958) used in the closing credits.
After Susan saves B.O.B., Link, and Dr. Cockroach from being crushed on Gallaxhar's ship, Dr. Cockroach says "By Hawking's chair." This is a reference to Stephen Hawking, renowned academic who is bound to a motorized wheelchair due to amyotrophic lateral sclerosis, also known as Lou Gehrig's disease or ALS.
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 trivia item 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'.