The intro sequence of the show has a bit where Grim's head is ablaze and laughing with a swirly background behind him, referencing the intro to Grim and Evil, back when the series shared a timeslot alongside Evil Con Carne.
Several examples involving Dungeons and Dragons. "Wand of Magic Missile — I'm never gonna use that thing..." said offhandedly by Grim as he rummages through his trunk of magic stuff in the basement. Obviously a reference to 2nd Edition D&D as wands of magic missile in that version of the game really were useless.
A subtle one in the Wrath of the Spider Queen special with the dark elves working for Velma Green.
Later in another episode, Skarr's mutation makes him resemble the eponymous alien minions from Pikmin.
He's also a parody of Herr Starr from Preacher, being a bald, one-eyed villain subject to various humiliations throughout the series.
In "Billy and Mandy Vs. the Martians", Grim casts a spell that gets Billy's nose stuck to an alien space ship. When Billy asks him to cast it again to undo it, Grim says he can't because it has a ten minute cooldown.
And in the movie, during the race in River Styx, you can actually hear the Monkey Island theme playing, maybe.
In "The Firebird Sweet", Grim directly references the 1939 movie Drums Along the Mohawk when the group was about to enter a factory via the sewer... then says that he was referring to the director's cut when Mandy questions the authenticity of his claim.
Mandy (off-camera) smells smoke after Grim and Billy accidentally torch the carpet. Mandy tells them that if she finds a scorch in the carpet that "I'm opening up a can of Powerpuff on you two." Also, in the Kids Next Door crossover, Billy answers the door, sees the Kids and says "You're not the Powerpuff Girls!" It's worth noting that The Powerpuff Girls was originally intended to target an older audience. And it was going to be called "The Whoopass Girls". Now take what Mandy said, replace "Powerpuff" with "Whoopass", and it all makes sense.
"Alas, poor Grim! I knew him Billy!" They get it closer to the real thing than most people, who substitute "I knew him well" for "I knew him Horatio", or some other variant.
Princess Morbucks was spotted in the background in the beauty pageant episode.
Sperg tossing Billy's bicycle over a sidewalk cliff, "This is Where the Sidewalk Ends Baby!" The cliff is also a reference to the book's cover.
In Big Boogey Adventure, the Boogeyman goes into a pipe, complete with the Warp Pipe sound from Super Mario Bros.
In one episode, Mandy demands that they leave the beach because she's tired of, among other things, an annoying dog that won't stop biting the back of her swimsuit, a la Coppertone (thankfully, Mandy is wearing a one-piece suit).
In the episode "Crushed," Mandy receives a makeover a la Sandy from Grease, with a heel-crushed lollipop in place of a cigarette.
In the episode "Smarten Up" Billy’s cat Milkshake eats an intelligence enhancing bookworm that was meant for Billy. After Billy complains about never being able to pass a math test now that the worm is gone Milkshake states “…I'm very well acquainted with matters mathematical. I understand equations, both the simple and quadratical.” These are lyrics from the “Major-General's Song” from the 1879 opera The Pirates of Penzance.
Also from "Grim in Love": Malaria and Grim dance the twist in a scene almost exactly like Mia and Vincent's in Pulp Fiction.
Sperg's band Purple Filth is likely named after the real metal band Purple Popcorn.
Mandy's line, "We accept you. We accept you. One of us." is a shout-out to the lyrics of "Pinhead" by The Ramones, itself a shout-out to the 1932 film Freaks.
A lot of the random lines that Mandy says after the opening titles qualify as these. Another example is when she says, "The call is coming from inside the house." This is a shout out to the famous Wham Line from When a Stranger Calls.
When Billy is asked what weapon he wants for a roleplaying adventure, he shouts "Warhammer!".
Nergal and his Nergalings might be a shout-out to Warhammer 40,000's Chaos God of Decay, Nurgle. Nergal's words to his son about romance sound suspiciously like Nurgle's attitude toward Isha, whom he imprisoned in his lab. Both beings are the namesakes of the Sumerian deity Nurgal.
Billy sees what looks like the shadow of a giant spider on his ceiling. He looks down to see that it is just Bubbles' stuffed octopus on top of his lamp.
One episode has a bunch zombies in a plane which has Air Voorhees written on its side.
At the end of "The Really Odd Couple", Mandy seals Billy in his closet behind a brick wall a la "The Cask of Amontillado". While she's doing so, Billy mumbles something similar to Fortunado's line "For the love of God, Montresor!" behind his gag.