Minor example, but some fans have noted that most ghosts caught in the film seem harmless until the Ghostbusters get involved. The ghosts in the game are generally far more dangerous. After all, in a game, the enemies need to attack you, don't they?
The black slime golems considering you fight two of them in cramped locales while being blasted by venom crawlers.
Possessor ghosts: not only do you have to remove them from their human hosts before actually busting them, but they can also turn the other Ghostbusters against you as easily as they do any other human. Expect a lot of running and sliming to keep yourself alive.
There's the Grave Golems that make the Black Slime Golems look like patsies.
Evil Is Sexy: The Spider Witch in the Realistic versions of the game. You wouldn't have guessed from her slashed mouth with fangs, unless you're into that, but in life she was a bizarre yet attractive woman. This was her main way of attracting her victims.
Goddamned Bats: Has this in the form of flying books that screech like bats. The spider chandeliers qualify too, but they're not nearly as annoying as the Book Bats who come in much greater numbers. The presence and, in later levels, commonness of "little destroyable ghosts" is a commonly-stated strike against the game.
Any time you get knocked over and subsequently revived by one of your team mates. There is something very sweet about having your childhood heroes actually coming to your rescue.
In the back of the Firehouse, you can find a giant plaque reading “Thank you Ghostbusters” from a class of 3rd graders, covered in green hand prints and drawings. Words cannot describe how adorable it is.
Most Annoying Sound: Listening to Peter Venkman repeat the same catchphrase "Little help" every time he's downed by a ghost and requires healing will get a little grating on a few players.
Nightmare Retardant: The Juvenile Giant Sloar, when looked at from a certain point of view, is Gypsy on steroids (and possibly roaring drunk, too, what with all the puking it does). Shandor's Destructor form can be seen as this, too: all the potential possibilities, and he limits himself to a stereotype cartoon devil.
Possibly as a result of how stereotypical the devil form is, the "creepy robed man" of the stylized version comes off as legitimately more menacing.
No Problem with Licensed Games: A very deliberate and intentional aversion of the usual "licensed video game" problems, thanks to the participation of the original cast and crew. Many fans consider it the true third movie of the series, especially in comparison to the reboot.
Porting Disaster: The PC version has no multiplayer. While that can be ignored, what can't be ignored is the horrid mouse acceleration that makes it unplayable unless you use a controller (or use 3rd party fixes, fixes that assume you have a Logitech-brand mouse).
The PC version also has no achivements, unlike the other Realistic versions.
Take That, Scrappy!: Slimer gets abused a lot throughout the game. In the main campaign, he's the Warmup Boss you get to beat up and force into a trap as he screams in fear. In multiplayer, there's a game called "Slime Dunk"; a whole section dedicated to you and other players beating up an entire legion of Slimers by flailing them around and shoving them into many traps painfully.
Tear Jerker: Getting knocked down while rushing to revive your team mates can be frustrating for most players, but devastating for long-time fans. You failed the Ghostbusters.
Likewise, getting knocked over and having to listen while the others are slowly beaten, unable to help them.
That One Achievement: "Nice Shootin', Tex!" Complete the game with less than $100,000 in property damage. How hard could that be? For reference, it's easy to exceed a million dollars in damage in the Times Square level alone.
That One Boss: Azetlor. He can move fast, has attacks that can drop you, Egon, and Ray in very few hits, has some of the highest health in the game, a fairly small vulnerable area, and can summon Book Bats to help him. Many Rage Quit at this point. You need to move fast and continue reviving your teammates if you intend to survive The Collector.
They Wasted a Perfectly Good Plot: The game is designed to evoke nostalgia and recreates a lot of famous moments from the original film. The unfortunate result is that all three 'movies' end up having the same basic plot with a new coat of paint, and the game sometimes comes across as a trip through an interactive "greatest-hits" reel.
And going in the opposite direction, while the film is not ignored, no scenes are recreated from Ghostbusters II. A rematch in the courtroom or the haunted tunnels could have been a lot of fun.
Uncanny Valley: The realistic version of the game on the PS3 and 360 renders most of the characters fairly close to the way the actors looked in the movies. While it is still somewhat stylized, there are more than a few moments that look almost life-like.
In some of the cutscenes using the game's graphics as opposed to CG, the Ghostbusters tend to move more like marionettes than people, and it's a bit unnerving. Even when the animation is good, people tend to find Ray to be the most unsettling due to the fact that the developers paid so much attention to making the characters look like their actors circa 1991 that they not only included Dan Aykroyd's Mismatched Eyes, but got the right colors on the right sides of his face (left eye brown, right eye green). Realistic faces + jerky animation + often-questionable lipsyncing = unsettling character models.
Vigo the Carpathian, the Big Bad of Ghostbusters II, is reduced to nothing more than his painting in the game, unable to do much of anything except talk. To add insult to injury, the painting is owned by the guys who beat him—the Ghostbusters.
The game also made Stay Puft much weaker than before, to the point the player character can take him on. It's actually stated in the game that Gozer's second manifestation as Stay Puft was much weaker than the first.