In the "Mercury Mines" level of Duke Nukem 1, Dr. Proton issues a taunt via a monitor:note The Duke Nukem 1 engine is very similar to the Commander Keen: Invasion of the Vorticons engine, as evidenced by playing both for at least half an hour each, and probably explains why the credits for Duke Nukem 1 include Tom Hall.
"Why bother Duke? Not even Commander Keen could survive the perils of my Mercury Mines!"
E2L7, "Lunar Reactor" contains a mutilated Luke Skywalker hanging upside down in stormtrooper armor.
"Now this is a force to be reckoned with!"
E2L8, "Dark Side", includes the monolith from 2001: A Space Oddysey near the end.
E3L1, "Raw Meat", starts with Duke sprouting the infamous Chew Bubblegum line. He can also sing "BOOOORN TO BE WIIIILD" in the karaoke.
E3L4, "L.A. Rumble", has a building that crumbles due to an earthquake looks exactly like the building where id Software's offices are in. While the building crumbles Duke will state "I ain't afraid of no Quake!"
E3L5, "Movie Set" is a movie set where a film based on the previous episode is being filmed. The helicopter that crashes at the start hits a water tower (a possible shout-out to Warner Bros, there). The poster for the film shows up in a couple of later levels, too.
E3L7 is named "Fahrenheit", the music is called "233C" and a fire engine is numbered "451". All of these are references to Ray Bradbury's Fahrenheit 451.
E3L8, "Hotel Hell", has a secret area, found by entering behind the pool's waterfall, where Indiana Jones is speared.
"We meet again, Dr. Jones."
E3L11, "Freeway", includes a flattened Terminator in a compactor. When you go inside for a look:
Near the end of the level, the player will face a police car on its side with the number 54. This is an homage to Car 54, Where Are You?
The Playstation port (Total Meltdown) has a control scheme called "Doomed", named such because it's based on the default control scheme of the Playstation Doom port.
The same port also add a new episode which features a few levels spoofing popular Playstation games: "Nightmare Zone" is based on the first level of Tomb Raider, "Trackside Tragedy" parodies Wipeout and "Gates Motel" pastiches Resident Evil and horror movies.
Duke Caribbean: Life's A Beach
The recurring boat is titled Kobayashi Maru. Three guesses where that comes from.
The title theme for the expansion pack is based on the Hawaii Five-O theme.
Also overlaps with Take That, aimed at God Mode, as the Marine says "Duke, we got your green power armor!" just before Duke snarks at him.
Duke comes across an EDF soldier who knew Duke's retirement "bullshit was just bullshit". He then goes on in a mocking voice about how he just helped one of his friends find his wife and calls his friend a pussy.
The first level of the game is a boss fight against the Cycloid Emperor, last boss of the third episode of Duke Nukem 3D, taking place in the very same stadium...sort of.
The "Balls Of Steel" edition and the achievement of the same name might be references to an old 3D Realms pinball, and a Shout-Out to a line that quickly became memetic due to a harassment video where Duke's voice lines from Duke Nukem 3D were played to infuriate a Ventrilo server admin.
"I'ma kill you old style!" is a reference to said harassment.
Duke's autobiography, "Why I'm So Great," was first mentioned in Duke Nukem II.
In the First Access Demo, when exploring some mining tunnels, as Duke breaks through wooden barricades, he declares his need for a crowbar in a situation like that.
The Railgun in the First Access Demo looks and sounds suspiciously like the Quake III: Arena railgun.
The Railgun in the released game, when zoomed in, uses the same scope overlay as Call of Duty 4's sniper rifles.
The twins that appear in the game are called the Holsom twins, alluding to the Olsen Twins. This is not the only reference they are to, however, since their multiplayer reward description is "2 Girls, 1 Duke", referencing infamous Shock Site 2girls1cup.
The ending is a parody of Jackson's death and the ending of Call of Duty 4: Modern Warfare, to which Duke replies "What kind of shit ending is that?"
Sometimes, if Duke steps on a rat, he'll say, "See you later, Mickey!"
The girl in the Duke Burger kitchen may wonder if "there'll be another season of Lightning Bug."
Behind the set of the "Damn It's Late Show" there's a stage hand getting berated by an angry actor for walking across the stage during filming, a parody of Christian Bale's infamous rant on the set of Terminator Salvation. Duke can even punch him out:
The donkey in the safety video in Area 51 and outside the Burning Bush refers to the 1999 iteration of DNF, where Duke would've met an old miner named Gus, who would've lent him his donkey to reach the bottom of the Grand Canyon.
The Impregnader is a weapon that works exactly like the GES BioRifle.