A monk that looks suspiciously like Jean-Luc Picard dwells on the island of Entrana and builds a balloon "to explore new frontiers". The balloon is then destroyed by Larry, Moe, and Curly.
Quiz #4 in the polls, question 7: "What slash defence bonus does the Corrupt Dragon chainbody provide?" One of the possible answers is "Over 9000".
When Bob gives you your second explorer's ring, he'll mutter about how "Adventurers these days are spoilt rotten. Why, in my day... (mumble)... dragons...(mumble) ...bare hands.
There is an NPC in the Herblore Habitat by the name of Astlayrix. His examine info is "He'll never give you up and he'll never let you down."
When giving thieving advice, Darren Lightfinger tells the player:
"It's the eye of the kyatt, it's the will of the heist."
When Jagex declared their intention to add new abilities to the Ring of Wealth, they prefaced the announcement with "RoW, huh, what is it good for?"
The examine text for Lumberjack Leif (an NPC on Miscellania) is "He's a lumberjack and he's okay." Additionally, two woodcutting-related Tasks are titled "I'm a Lumberjack and I'm Okay" and "I Sleep All Night and I Work All Day".
In the old version of the "Wolf Whistle" quest, your character, asked to kill a Wolpertinger, responds "One rabbit stew coming up!" in a reference to the Monty Python and the Holy Grail killer rabbit scene. The Wolpertinger familiar's examine text is "It's just a harmless wee rabbit."
If you speak with Bob the Cat while your own cat is with you, the two cats will re-enact the dialogue from the Luke, I Am Your Father scene in The Empire Strikes Back. Similarly, if you type "I am your father" into your in-game notepad, the note that shows up will instead say "Nooooooooo!"
Bork, the Big Ork, summons Ork Legions that spout Borg catchphrases like "Resistance is futile!" and "We are the collective!"
If you perform poorly in the Great Orb Project minigame, one of the wizards will comment that "This was a disaster! I'm making a note here: HUGE FAILURE." Additionally, the examine text for the portal that transports you between Runecrafting altars is "Look at you, examining things when there's Runecrafting to do." And in the "Meeting History" quest, the examine text for a portal is "There is cake in here, apparently."
The clock above Catherby's bank is stopped at 10:04, a reference to Back to the Future.
The Fairy Godfather's henchmen Slim Louie and Fat Rocco both have examine texts that quote Goodfellas.
The monkey bars in the Brimhaven Agility Arena have examine text that quotes "I Wanna Be Like You", the monkey song from The Jungle Book. The pillars have the examine text "A small step for a player, a giant leap for player kind," a quote from Neil Armstrong, the first man on the moon. The poison darts have a Bullet Time dodge animation referencing The Matrix.
The Flared Trousers item changes your "Dance" emote to one used by John Travolta in Saturday Night Fever. Their examine text is "These'll help me stay alive."
One of the smaller pigs in Draynor Village has the examine text "I shall call him...Mini-Pig." The same reference is duplicated in the examine text of the baby moles in the caves underneath Falador garden.
The "Zombie Dance" emote is one of the dance moves used in Michael Jackson's Thriller music video. The examine text of the Zombie Boots is "Thrilling!"
In Dungeoneering, you can get an award for being killed by a Bovimastyx dinosaur. If you do, you'll be treated to a Jurassic Park quote.
Edgar Allan Poe's short story "A Cask of Amontadillo" is about a wine connoisseur named Fortunato. The wine salesman in Draynor Village is named Fortunato; his examine text is "He looks as if he could do with a sip of Amontillado."
Naturally, the Raven pet's dialogue contains additional Edgar Allan Poe references.
If you give a cowbell to the penguin musicians Ping & Pong, they'll use it to play a song. Afterwards, they'll note that it needs more cowbell.
The "What Lies Below" quest includes an NPC archaeologist named Louisiana Jones. Similarly, the quest "Desert Treasure" includes Asgarnia Smith, also an archaeologist.
Rock Lobsters are monsters that can be found in the Waterbirth Dungeon. Their examine text is a line from the The B-52's song "Rock Lobster."
Many of the Tasks contain Shout Outs to other works.
Smithing a bronze mace rewards you with the Mace Invaders achievement.
Speaking with the Duke of Lumbridge awards you "Hail to the Duke, Baby", a Duke Nukem reference.
Killing an enemy on the Khazard battlefield completes the "Dukes of Khazard" task.
If you use the Ring of Charos to magically enhance your powers of persuasion, you can unlock "These Aren't the Coins You're Looking For" by convincing the sailors to give you a free ride to Karamja. There's also "TzHaar Wars" for playing a minigame in the TzHaar area.
Speaking of "A Clockwork Syringe", the final part of that quest is essentially a big shout-out to BioShock. You have to infiltrate a facility disguised as what's essentially a Pirate Zombie Big Daddy, and just in case we didn't get it, the examine text for one of the enemies reads "Would you kindly kill these slicers?"
The Christmas 2011 Event has you gather ingredients for a bunch of goblin chiefs. You placed the ingredients in a cannon and it begins firing out of control. The goblins get hit, but your character dodges the shots by backflipping Matrix style.
Estocada, the Badass Spaniard who gives out duellist's caps at the Duel Arena, has dialogue based on The Most Interesting Man in the World, including such lines as "I don't often replace hats, but when I do, I choose to replace duellist's caps." and "Stay victorious, my friend." As a bonus, his examine text quotes a line of Inigo Montoya's dialogue from The Princess Bride.
Zachory Bragg, of the Temple Trekking/Burgh de Rott Ramble minigame, has a personality loosely based on Zapp Brannigan of Futurama. His dialogue includes several Brannigan quotes, like "Be careful; this whole area is uncharted. But that might be because I lost the chart."
You can knock on a door in the west Varrock bank, and someone asks who's there. This is a setup for a knock-knock joke, and you're provided with three responses. One of them is "Doctor".