The opening of Angry Video Game Nerd Adventures shows an image of the ScrewAttack website logo on a television screen. Due to James Rolfe leaving ScrewAttack shortly after Adventures' release, the Deluxe version of the game replaces the image with one of 7 Grand Dad, a bootleg that gained infamy after Adventures' release for its bizarre mashing of Super Mario and The Flintstones characters.

Notably, the Angry Video Game Nerd has yet to review either 7 Grand Dad, its unmodified form as The Flintstones: Rescue of Dino and Hoppy, or any bootleg graphical modification ROM hack.

At the end of each level, the game shows a congratulations screen that is purposely misspelled as "conglaturation!"

This is a reference to the NES game Ghostbusters, and the infamous ending screen which misspells congratulations the same way.

The Boss of "Dungeons & Dickholes" is based on a creature from the movie "The Giant Claw".

The same creature was also feature in another FreakZone game, Manos: The Hands of Fate, as a Boss named "Battleship Bird" from End Credits.

The Game Over Screen of AVGN Adventures is based on a Game Over Screen from Friday the 13th on the NES, reading "You and your friends are dead. Game Over". During the review for the game the Nerd suggests making it even more severe, and suggests;
"You're dead. Your friends are dead. Your family's dead. Your fucking pets are being skinned alive. Your mom's a fucking whore. You suck at life. The whole world hates you. You're going to Hell. Live with it. Game Over."

The design of the poop spitting monsters found in the Thy Farts Consumed level are based on the Cacodemons from the Doom series.

The moon from The Legend of Zelda: Majora's Mask appears in the background of the Assholevania level.

The beginning of the Boss Battle theme sounds extremely similar to a segment of the track: "Porky Means Business!" from EarthBound.

The final boss, Spoiler:"Fred Fucks" is based on Spoiler:"Fred Fuchs" whose name was in the credits in the video game Spoiler:"Bram Stoker's Dracula" based on the movie of the same name. In the Angry Video Game Nerd Spoiler:Dracula episode, the Nerd jokingly pronounced the word Spoiler:"Fuchs" as "Fucks".

The game's final stage, "Laughing Joking Numbnuts", is based on ##LJN##'s logo, and the name that the Angry Video Game Nerd has adopted for the company.

The level, "Beat It & Eat It," was originally made with 16-bit style graphics before it made the switch to Atari graphics.

The level Boo! Haunted House is named after the Nerd's nickname for the Nightmare on Elm Street NES game.

The "beginner's trap" the Nerd made up in his Super Pitfall review appears in the Dungeons and Dickholes level, appropriately down the first ladder in the level.

In early builds of the game, Guitar Guy's sprites were designed after his actor in the web series, Kyle Justin, complete with dialogue referencing his appearances as a guest reviewer. However, the final game redesigns his sprites to depict him as a skeleton, referencing a gag in the Ikari Wars review where the Nerd discovers that Guitar Guy died and decomposed behind his couch before reviving him with a cheat code from the NES game. Likewise, each of Guitar Guy's lines is replaced with an ellipsis.

In a post on the game's Steam Community page, BlackFlag, one of the developers, stated that the redesign was mutually agreed upon following discussions between Justin and the development staff.

Arin Hanson, also known by his alias EgoRaptor, can be found hiding atop a cloud in the level "Blizzard of Balls". When talking to him, he'll say "Don't be a Grump, take these!" which the Nerd will say "Thanks, EgoRaptor. Now I'm not so Grump!". The dialogue is a reference to the web series Game Grumps which Arin co-hosts.

The level "Future Fuckballs 2010" is based on the game Street Fighter 2010 which the Angry Video Game Nerd had previously reviewed on his show.

When Angry Video Game Nerd Adventures launched on Wii U, the Miiverse page initially allowed screenshots from the game to be posted, which led to many users using the game as a loophole to post profanity. Shortly after, the ability to post screenshots would be removed.