* When a player becomes infected, the screen goes trippy and blue and you are forced to endure the slow and heavy breathing of your character as they slowly become a zombie. It's not a pleasant sound.
* The bizarre object in the background of the main menu. It looks like a monster fetus, possibly a Licker.
* [[spoiler: The screen fading to black just before whichever character you're playing as shoots Claire in the head [[KickTheDog right in front of Sherry Birkin]] and [[EvenEvilHasStandards if you're playing as Lupo you can tell by her tone she does not want to kill Claire in front of Sherry]] should you choose to execute Leon.]]
* Vector's unique "Active Camoflauge" ability that renders him nearly invisible. Something about not seeing a guy ready to plunge a knife into your throat before death is kinda unnerving.
* USS Command. [[BadBoss Unforgiving]], cruel, quick to lose his temper, extremely psychotic, and [[spoiler: ''will'' leave you for dead in a zombie infested city to fend for yourself like a common citizen for being unsuccessful in your mission even if it's not in the slightest your fault.]]
* The new NE-Beta parasite B.O.Ws and Parasite Zombies exclusive to this game. These bugs are essentially the adult form of the same parasite put into the Nemesis to make it under Umbrella's control and follow simple orders. They're pretty gross and creppy by themselves, but then one crawls on the nearest zombie's back, ''bites off its head'', and then commandeers its body like a robotic suit.
** [[spoiler: One of them pulls that on a ''TYRANT'' in a late Spec Ops mission.]]
* Remember what a total pain and [[NightmareFuel terrifying]] enemy Mr. X was in VideoGame/ResidentEvil2? Now you get to fight two of them ''at the same time''. [[SarcasmMode Doesn't that sound like fun?]]
** Remember how much ''more'' terrifying it got when it lost it's [[PowerLimiter coat]] and became the FinalBoss Super Tyrant? Have fun fighting ''four of them at the same time''!
* The mission briefing cutscene, where you finally see exactly how screwed the city really was before Leon and Claire arrived.
** It's a toss-up over which is worse: the footage of people being attacked, or the radio chatter which includes:
*** A 911 call from a hysterical woman crying that "He's trying to get in through the windows!" before the call cuts out. For added horror: [[RapeIsASpecialKindOfEvil that may not have been a zombie]].
*** The police trying (and failing) to save the civilians.