- A particularly cringeworthy funny moment in Resident Evil 5: during the first battle with Wesker, he may at certain points suddenly shout "Your future HINGES upon this fight!" and then literally kicks you through a door.
- Speaking of Wesker, the beginning of the second fight with him where he takes off his sunglasses and throws them at Chris, and Chris catches them with an epic WTF look on his face before Wesker shoulder checks him.
- The moment you realize that one piece of the fight requires you to turn off the lights so he can't see you is liable to make for an amusing surprise.
- For a contest, someone made a Johnny Bravo soundpack for Wesker. You may never be able to take him seriously again.
- When you're exploring the ship, you can actually stop by the bridge, where the captain's chair is. Interacting with it has Chris/Sheva sitting in it and saying something one wouldn't normally say given their situation, before stating that they need to get going.
Chris: "Always wanted to be a captain, but now's not the time."Sheva: "What a comfy chair."
- In the third part of Chapter 2-2, you find a port-a-potty just sitting there for no apparent reason. If you walk up to it, the two options you have are simply labelled "?". Pressing either button causes either you or your partner to knock on the door. As soon as you back away, the door opens up, revealing that a Majini was inside.
- DLC gives us a few new costumes as well as new figurines to go along with them. When you manage to get the figurine for Chris' new "Warrior" outfit, well...
- What's the achievement for knocking an arrow out of the air with your knife?
Be the Knife
- There's a part during the Final Boss battle with Wesker where Chris punches a boulder with his bare hands. That part became meme worthy.
- During the Final Battle with Wesker on the volcano:
Wesker: The human race requires judgment!Chris: And you're going to judge us? Do you get all your ideas from comic book villains?