Compared to how quick and dangerous he was in Resident Evil 3: Nemesis, Nemesis is a bit disappointing in ORC, apparently content to stomp around slowly while firing his minigun. He's a little closer to his classic self in the Echo Six DLC campaign, but still nowhere as fast or dangerous as he was in RE3.
The fight with two Mr X, if you know what you're doing.
Demonic Spiders: Hunters and Crimson Heads. Both are extremely fast and will mercilessly pin you down and claw at you until you're dead. It doesn't help that Hunters in this game have armored backs so you have to attack them from the front and can take around two clips worth of ammo to bring down.
Almost literally in the case of the NE-Beta Parasites. They are very quick and on their own, are easy to kill, provided you can hit them. However, if you don't hit them the moment you see them, they will climb up onto the back of any one of the dozens of zombies around and rip its head off to hijack its body. They move with the speed of Crimson Heads, and if you just target their bodies the parasite will skitter off to hijack another body. There are usually three or four of these running around where you encounter them to boot, all of them out to commit grand theft zombie.
HUNK of course, who actually manages to be even more badass in this game then he ever was in the series before.
Vector became this well before the game even came out. It certainly helps he was trained by HUNK himself and looks a good deal like him (with the gas mask). Hell, he's the most composed member of the team and says pretty badass stuff.
Nemesis, which fans were more than happy to see a return of.
Evil Is Sexy: Lupo, Four Eyes and Bertha all qualify. Despite wearing gas masks, a good deal of Lupo and Four Eyes facial features can be seen and they're quite easy on the eyes. Not to mention Lupo wears skin tight leather. Bertha's face is completely covered, but some of the lines she says, how excited and eager she becomes when she sees her situation like a game and her accent make her just as sexy as the other two.
Fanon: Despite ORC's status as a "gaiden" game, the characters, particularly the Wolfpack, have proved popular enough that they're often worked into 'fic.
Funny Moments: If Nicholai suffers friendly fire during a Heroes mode match, he will loudly complain, "Did you just shoot me?!"
Game Breaker: The Super Soldier active ability is essentially a win button, which reduces many multiplayer matches to a question of how good your Leon, Lupo, Nicholai, or Dee-Ay happen to be.
Goddamn Bats: Zombies. They are everywhere and unless you shoot them in the head, they soak up your ammunition. A room full of them will deprive an inaccurate shooter of most of their ammunition. If you start bleeding, they swarm on you like sharks. And of course, they can infect you, which is a death sentence if you don't have an anti-virus. Fortunately, they only show a preference towards the closest bleeding human, U.S.S or SpecOps.
Memetic Badass: HUNK. William Birkin sure has some balls to take him on.
Most Annoying Sound: In the level where you need to retrieve the EMP devices after Nicholai shoots down the helicopter carrying them. The devices make a really annoying garbled/scratching sound that will drive you nuts if you don't find it quick enough.
That One Boss: Already people are stating that the double Mr. X Tyrant boss fight is the most difficult boss battle in the game. Sure it can be less hectic with a full team of players, but try and battle them both with no help.
The Super Tyrant bosses for spec-ops. Up to four super tyrants at one time, along with the typical zombie mob. Even worse, these tyrants have been speed-buffed and are each legitimate Lightning Bruisers. One of the few points in the game where you can just get stun-locked to death.
That One Level: Mission 5 is an utter nightmare. Hunters drop from the sky both in large groups and often, soldiers are thrown into the mix to make life that more difficult, and finally it's the two T-103s.
On any given preview of the game, you'll find multiple comments decrying the fact that Operation Raccoon City is radically different than the previous games in the series.
The faces of Jill and Carlos have changed. Fans of them are not happy.
They Wasted a Perfectly Good Plot: As stated above and on the main page, much of the pre-release information touted that the game would seek to alter Resident Evil's history by offering the chance to kill off the protagonists of the previous series', radically altering the series timeline. However, the final product only allows you to kill Leon Kennedy yourself and nothing is mentioned of how this would change the series. The Spec-Ops DLC makes this even worse, as your objective is to protect Jill and Carlos. Naturally, this was seen as a pretty big let-down.