Creative Differences: Surprisingly, the Nickelodeon executives actually (knowingly) let the writers get away with a lot of stuff. Character deaths that were originally written were never allowed, though.
According to Rikki Simons, this was more a problem between Vasquez and series director Steve Ressel than it was with any of the suits. Ressel wanted to go all-out with camera angles and cinematography while Vasquez wanted the gags to speak for themselves.
Outside of the Americas (Brazil, Mexico, USA); GIR is often voiced by a woman.
Zim, Dib and GIR are voiced by women in the Japanese dub
In "Halloween Spectacular of Spooky Doom", Nightmare Bitters was voiced by Rodger Bumpass.
God Never Said That: Unfortunately, the phrase "Jhonen said" has been falsely appended to so many baseless rumors that unless there is an actual verifiable citation included you're far more likely to be reading something someone heard Jhonen said from someone else who who heard it and so on... following the Gossip Evolution back to its source often leads only to the reveal of glorified fanon whose origin had been lost in the telling. According to (note the citation) Jhonen on his blog, even Wikipedia and IMDB have included errors by not sourcing, meaning you can't necessarily trust everything you read there too. While not every person who makes the claim to Word of God without citation is incorrect, you should adjust your credulity accordingly.
One of the most common assertions to fall under this clause is Zim being 16 in "Irken Years" and 150 or 159 in human years. Word of God on the age business is that Zim is older than any human alive, but fanon, perhaps not liking the extreme age gap between the show's main protagonist and his chief rival, invented the concept of "Irken Years" putting his "relative" age far closer to Dib's, and his real age closer to the lower bound of "older than any living human". Somewhere along the line this made the jump from fanon to false Word of God. You won't find any interviews or blog posts verifying this fact, although some user-edited information sites such as Wikipedia have listed it from time to time (entries inevitably being deleted due to the lack of citation).
The biggest one, perhaps, is that it would take a crapload of money for Vasquez to even consider coming back to the show, often attributed to the man himself but actually a rumor spread by series directorSteve Ressel, who had his own issues with the way things were run. (Vasquez does often make disparaging remarks about Zim, but the same way he does about everything—with his tongue superglued to the inside of his cheek.) One would think Vasquez's presence on most of the DVD commentary tracks and his offer to do cover art for the DVDs would assuage this, but alas. Recently his blog posts and appearance at InvaderCon II have been doing more to dispel the rumors.
Ultimately, my idea was to take his sights off world domination, as ZIM begins to understand that there is a beauty in human life, an understanding that sets him on his path to becoming a public legal defender. I was very inspired by Ben Affleck's powerful courtroom scenes in Daredevil, and I wanted to move people to tears like those scenes moved me. But the show was canceled before any of that, thus leaving our audience of ten unfulfilled.
If that is not ridiculous enough on its face to give away the game, the Daredevil film came out in 2003, a year after the show's cancellation, meaning the quote literally cannot be true, and "moved to tears like those scenes moved me" is almost certainly meant as a Stealth Insult. See also The Walrus Was Paul.
Orwellian Editor: The commentary tracks only ever acknowledge director Steve Ressel's Creator Cameos as "Joe the janitor", if at all, due to his feud with the writers and suits alike.
Production Posse: Vazquez moreorless hiring all his comic book author friends to do the show with him doesn't strictly qualify, but Rikki Simons (voice of GIR and color artist for the show) had previously done the color for I Feel Sick.
Screwed by the Network: Maybe not as bad as certain other Nick shows, but still a factor. The show was constantly jumbled all over the schedule so that nobody ever knew when it was on, and new episodes were premiered at timeslots like 9:15 pm. However, while the suits didn't always understand exactly what he was doing, they gave him an awful lot of leeway, and Vasquez himself would later admit that given complete creative control the only thing that might change was that extras would explode at random.
The first episode contains the line "Invader's blood marches through my veins like giant, radioactive rubber pants!" The line was supposed to say "ants". But it's the kind of show where "pants" actually fits better.
The Hamstergeddon episode involved Ultra Peepi swaggering down the street, not by intention. It came back from animation that way, and Jhonen loved it and had the composer make funk music to go under it. "I want to hear Barry White saying 'Ultra Peepi.'"
Another instance of one of Zim's fubbed lines being kept in the show: in 'Bad, Bad, Rubber Piggy' Zim says the phrase "temporal doom." It's technically supposed to be pronounced temp-er-al, but on every take Horvitz would only say temp-ohr-uhl. After a few takes they realized they wouldn't be able to get him to say it correctly, so they kept the line in.
Danielle Koenig's original script for "Vindicated" had Dwicky genuinely believing Dib. She refers to the change as Jhonen having "mangled" it, but she didn't sound as annoyed about it as her word choice might lead one to believe.
It's claimed in the commentary that the original ending of "Bad, Bad Rubber Piggy" was Dib dying and being replaced by a character named "Louie" as Zim's new rival. This may have just been a joke, however.
Another commentary tidbit is that Iggins was originally slated to die at the end of "Game Slave 2," but Executive Meddling prevented that.
In a blog post Jhonen noted the original script for "Gaz: Taster of Pork" simply ended with Dib defeating the Porklord and then sharing pizza with Gaz. Eric Truehart came up with the ending we got instead.
Mark Hamill was originally considered for the role of Zim, but was dismissed by Nickelodeon for sounding too old.
Billy West was also considered, and his voice is Zim's in the original pilot, available on Youtube. However, with Futurama already on the air, Jhonen didn't want West's voice in two sci-fi shows at the same time, citing it to be too recognizable across both shows.