Dana Barrett was originally in the script, but Sigourney Weaver turned down the offer to play the role. However, Weaver changed her mind when the rest of the films cast, including Bill Murray, were signed on, but by that time, Dana had been written out and the part had been rewritten as Dr. Ilyssa Selwyn (played by Alyssa Milano).
A monitor in Egon's lab displays, "Conglaturation!!! You have completed a great game. And prooved the justice of our culture. Now go and rest our heroes!" This is the endgame text from the original Ghostbusters video game for the Nintendo Entertainment System, typos and all.
At one point if Sigourney Weaver had taken a role in the game she would have been the voice of the Ghostbusters computer. The explanation would have been that Egon had programmed it with Dana Barrett's voice to annoy Venkman.
Ghostbusters on the Wii and PlayStation 2 uses a stylized take on the famed characters instead of trying to replicate the look of the realistic versions of the game. That style was inspired by the work of an independent artist by the name of "Dapper" Dan Schoening. Dan Borth, the CEO of Red Fly Studio, has stated that when his team was first approached to do Ghostbusters, Vivendi/Sierra (the game's publisher at the time) gave them a large group of concept and fan art to go through, which included Dan Schoening's work. Mr. Borth first contacted Mr. Schoening to work on an unspecified project. After many months of no communication from Red Fly, Dan Schoening found art online for the stylized version of Ghostsbusters that looked remarkably similar to his own designs. Mr. Schoening then contacted Red Fly and confirmed his designs were used. An agreement was reached that included money and an on-screen credit. Although he was 100% guaranteed an on-screen credit, the game was released with Dan Schoening's name nowhere to be found - not even as a Special Thanks. With the agreement not being upheld, Mr. Schoening posted a message on his blog about the matter, which was then picked up by several of the top gaming sites. In response, Red Fly put up an apology to Dan on their blog. Then Mr. Borth felt the ill advised need to "defend" himself in a written response to gaming site Kombo. Luckily for all involved, that didn't escalate things any further.
With the game becoming a major commercial success, Dan Aykroyd admitted that its plot is essentially what a proposed Ghostbusters 3 film would have been, now made impossible as is with the death of Harold Ramis.
Louis Tully was originally planned to be in the game, but because of hardware limitations, animating him alongside the other main characters was impossible, and the only way they could've had his character in the game would have been in a wheelchair completely incapacitated in a full body cast. It would have been explained he got injured in an accident and was recovering. When Rick Moranis turned down the role, the part was removed.
At one point in the game, if you check the voicemail machine upstairs you'll receive a message from a Professor Jones who inquires about the whereabouts of the Vigo painting, saying that it's priceless and that "It belongs in a museum". This is an obvious reference to the Indiana Jones movies.
An in-game screen shot of Egon's lab had a child's drawing hanging up in the background. It is a crayon drawing of a Ghostbuster firing his proton pack. The words under it read, "To Uncle Egon, from Ed." This could be a reference to Ed Spengler from the fan films Freddy vs Ghostbusters (2004) and Return of the Ghostbusters (2007). When the game is set to take place, Ed would have been just a child.
The Ghostbusters' theme is never fully played during the game, not even during the final credits of the realistic version (PS3/X360/PC). It is played in full during the end credits of the stylized version (Wii/PS2).
In the firehouse basement across from the containment system is a workbench where you will find a PKE Meter like the ones used in The Real Ghostbusters (1986) as well as the ghost traps used in Extreme Ghostbusters (1997).
The intro stage where the Ghostbusters were using their proton packs (trying to catch ghosts that escaped their storage facility) in their own HQ, was in an original concept from the first _Ghostbusters (1984)_ but never made it in the script where Ray, Peter and Egon testing their equipment (but not completely successful), though they mention this in the movie.
The game takes place 2 years after Ghostbusters II (1989). Ghostbusters II (1989) took place 5 years after Ghostbusters (1984), which means that the game takes place 7 years after the Ghostbusters battle with Gozer.
In issue #4 of the Ghostbusters comic series, published by IDW, it is revealed that the Rookie's name is Bryan Welsh in the realistic version and Chad Fuller in the stylized versions. In the stylized versions, the Female Rookie's name is Maddie Collins.
The trivia item below may give away important plot points.
At the end of the game, the Ghostbusters consider giving the Rookie character a chance to start a franchise so that there will be other teams of Ghostbusters across the world. This ties into Dan Aykroyd's original concept for the Ghostbusters. When he first pitched the script for the first film in the early 1980's, his original idea was that the film would be set in the future and that there would be teams of Ghostbusters just as there are units of fire fighters and paramedics.