Real Life Writes the Plot: The reason the Anti-Monitor gets almost destroyed by Supergirl and redesigns his armor halfway through the series was George Perez realized that the initial design of the Anti-Monitor was really impractical when it'd come down to an actual fight (he had large, cumbersome cables running alongside his arms and his mouth is literally wired to the front of his chest), thus recreating a much more practical design.
Running the Asylum: The later revelation that Marv Wolfman had more or less been dreaming about this since he was ten led to a lot of accusations of this (in the negative sense) being thrown around, re: The DCU being one man's plaything for his childhood fantasies. (It's worth remembering that all of the DC higher-ups at the time signed off on it, though, so any "blame" has to be shared among a number of people.)
The History of the DC Universe was to have been the final two issues of Crisis on Infinite Earths. It ultimately was published (separately), but a year later with new material referencing the events of "Legends" as well as a couple of spoilers for then-upcoming storylines (such as Captain Atom and Rocket Red joining the JLI).
Hal Jordan was supposed to die but was given a reprieve.
The story itself underwent numerous revisions: earlier versions omit the "dawn of time" angle for a big bomb, a contrived negating of the genocidal tone of the series by revealing that everyone who died on the destroyed Earths didn't really "die" but had their life energy and memories "merge" with their other universe counterparts, as well as establishing the plot point that the story's big "hero vs villain" showdown was the Anti-Monitor's doing due to him kidnapping ALL of the surviving Earths villains and forcing them to fight the heroes to distract them from stopping the bomb he was building.
One original idea for the ending would be the Superman of Earth-1 fighting the Anti-Monitor at the end and dying. Earth-2's Superman would then remove aging makeup, revealing that he actually had not visibly aged past adulthood. Then the original Superman would take the place as the "main" Superman again. However, this ending was rejected when John Byrne's The Man of Steel got greenlit.
It is stated in the Absolute Crisis companion that the only reason Supergirl's death got approved, was that the Helen Slater Supergirl movie flopped so hard and so badly, that no one at the corporate level would care that she died.
Marv Wolfman has stated that he had an out to bring Barry back: while running to his death in Crisis #8, he bounced around pretty much through a great number of points in time (as seen in the series itself) but during several of these "pit stops", Barry would not immediately be sent back to continue running, so long as he didn't use his super speed powers to run (as when he ran, he would randomly be picked back up and resume his death sprint. Barry would make one of these involuntary "pit stops" after the events of Crisis for an indeterminate length of time; the knowledge that any time he used his power to run, that Barry would risk abandoning his friends and family and continue onward to his death, would have a irreversible effect on Barry's personality as he realized that he he needed to enjoy what little time he had left and start enjoying life, before resuming said death sprint at any moment.