THE COMING OF GALACTUS ("Fantastic Four" #48)
Uatu The Watcher appears in Reed's lab to warn him of the world-eater, as seen in the classic story voted #19 in CBR's list of the Top 100 Comic Book Storylines. But he really should have knocked first, as Reed was using the sky full of space debris as a distraction for a little "alone time" with the Internet. There's no clearing your search history from an all-seeing, omniscient Watcher.
However, when the Silver Surfer lands on the Baxter Building's roof to summon Galactus, Reed's already there having a hella cool rooftop BBQ. Not that he bothered to invite the rest of the Fantastic Four. Before the Surfer can call his master, Reed offers him a beer made in his lab's microbrewery, where Negative Zone yeast and Unstable Molecules hops combined to form a knock-you-on-your-silver-ass brew.
Reed and The Silver Surfer keep drinking, eventually hitting up a few strip clubs and crashing the Fantasticar into a tree. Yggdrasil, to be precise. While the Earth is saved, Sue has enough and permanently leaves Reed for Namor. Though initially heartbroken, Reed eventually moves on with a revolving door of grad students, topless dancers and the occasional burlesque performer.
THE KREE-SKRULL WAR
Don't remember the details of this crossover? Neither does Reed. He locked himself in a dark room with 8 grams of dried Psilocybin mushrooms before the war broke out and missed the whole thing.
The upside is that his hallucinations would later help him make sense of The Clone Saga. He's been seeing multiple Spider-Men for decades.
THE INFINITY GAUNTLET
THE ONSLAUGHT SAGA
When decades of Charles Xavier's repressed anger manifest as the psionic being Onslaught, he uses an army of Sentinels to cut Manhattan off from the rest of the world. Onslaught's Sentinels are stopped by Reed's own army of A.I.s, from H.E.R.B.I.E.s to Ultrons to animatronics on loan from Disney World.
Once the smoke clears, Reed turns all the robots into an '80s cover band fronted by the Disney World animatronics called The Hall and Oates of Presidents.
When the Pro-Registration side needs an off-the-books prison to house captured unregistered superheroes, Tony Stark approaches Reed to request access to the Negative Zone. Unfortunately, the only suitable facility is already in use as a grow house where he's producing some primo weed.
Iron Man attempts to commandeer the grow house, leading Reed to ally with Captain America's Secret Avengers. But Cap rejects him -- apparently, partnering with a serial killing psychopath like The Punisher is OK, but Steve Rogers draws the line at pot-smoking mad scientists. Blame it on being frozen during the '60s.
Reed eventually decides to sit out the war in his grow house with some of his favorite customers -- The Impossible Man, Doctor Strange, Moon Knight (by prescription, that dude needs to mellow out) and, of course, Mary Jane Watson.
The news that Skrulls have infiltrated the superhuman community leaves the Marvel heroes reeling, wondering who they can trust. Luckily, Reed's used to dealing with heightened paranoia, and takes an active role leading the fight against the Skrulls.
When the Marvel Universe collides with the Ultimate Universe, Doctor Doom's sheer force of will harnesses the power of the Beyonders to hold existence together into a world he rules as a god. Eventually, Reed wrests control from Doom and recreates the universe, but with a few sloppy mistakes. The Earth he creates is a dystopia, where David Bowie and Alan Rickman die within a week of each other and Donald Trump has an actual chance of becoming President. Who'd want to live in a place like that?