As soon as the season five finale aired, many fans guessed that the decrepit mansion that Phantom Limb (and later, the entire Revenge Society,) used as their headquarters was really the childhood home of the Monarch, who was about to move back in with his wife and #21. The opening sequence of All This and Gargantua-2 confirmed it.
The Investors and Dr. Killinger being of the same species/class of beings/organization was another popular fan theory proven correct by All This and Gargantua-2 as well. The theory hinged on both having similar abilities, but who use them in different ways. Killinger acts a benevolent Trickster Mentor who helps his clients earn what they want most, and helps them make important realizations about themselves. Meanwhile, the Investors give their clients what the clients seek, but as part of a Deal with the Devil style deal.
One of Us: In the commentary for "The Diving Bell vs. the Butterglider", Doc Hammer and Jackson Publick mention several trope names before specifically stating that they read TV Tropes.
Pretty much every character has made some kind of geeky reference at some point. "What Color Is Your Cleansuit" reveals The Monarch and Dr. Mrs. The Monarch even have Cosplay sex. Although Dr. Mrs. The Monarch isn't a fan of Game of Thrones like her husband is, and thinks when he mentions Drogo, he said Drago, as in the Rocky character instead.
The Other Darrin: Professor Impossible has the most voices actors out of all the characters. (Peter McCulloch) voiced him in the pilot, Stephen Colbert played the part for two episodes in the first two seasons, then, due to Colbert not being available, Jackson Publick voiced him in a single season 3 episode, before Bill Hader took the part for three season 4 episodes. Finally, Stephen Colbert took the part back for "All This and Gargantua-2".
Rewatch Bonus: In "ORB", at the end of the flashback showing Col. Venture about to activate the ORB you can hear glass breaking, foreshadowing the reveal in "The Revenge Society" that Sandow broke the ORB instead of killing Venture.
Shrug of God: After an episode was made that strongly implied if not stated outright who the boys' mother was, the creators said that they're still not sure themselves whether or not she is, as they don't plan too far ahead with episodes and it just sort of happened.
Talking to Himself: Everycomedyduo in the show except for the Venture boys themselves (Monarch and Dr. Girlfriend, 21 and 24, the Murderous Moppets, Billy and White, Watch and Ward, Doe and Cardholder) are voiced by writers Doc Hammer and Jackson Publick; Publick also voices Hank, Sergeant Hatred, Action Man, Col. Gentleman, Ned, the Pirate, and Dr. Henry Killinger. He talks to himself a lot as a result. Doc Hammer does it the most often between Dr. Girlfriend and 21, while James Urbaniak gets in on the act with all Dr. Venture/Jonas, Jr. conversations. The season four episode "The Revenge Society" has Urbaniak in a three-way conversation with himself, but the writers try to keep the number of Talking to Himself instances down. For example, any time 21 and 24 interact with the Venture twins, 21 always pairs up with Hank so that Jackson Publick doesn't play both sides of the conversation; similarly, most of these characters are often kept inside their Cast Herds so that they do not interact with the voices most similar to their own (the Action Man has yet to talk to Sgt. Hatred, for instance, while 21 and Billy are always kept far away from each other).
Literally, at one point, when Hank makes a quick recording on his watch to describe his first time, before getting his memory wiped. Turns out he knows himself exceedingly well.
Throw It In!: Doc Hammer commented that it is impossible to stop H. John Benjamin when he wants to ad-lib, and as a result his dialogue is a middle ground between the original script and Benjamin's ad-libs.
Too Soon: "Handsome Ransom" involves a Captain Ersatz of Superman and Batman who takes a shine to Hank as his new Robin. It involves "sleepovers" and giving him lots of toys. For what it's worth, the season had started production beforeMichael Jackson died.
Troubled Production: The Venezuelan Spanish dub, big time: Besides the quality of that dub wasn't great at first place, only 26 episodes were dubbed, partly because Cartoon Network canceled the Latin American version of [adult swim] and partly because Dean's voice actor retired from voice acting at the middle of the series, so he was hastly replaced in the remaining episodes. While the series was resumed in a different network, it was broadcasted sub-only instead.
What Could Have Been: Listening to the creator commentary on some episodes is kind of sad once you hear how many interesting tidbits had to be cut for time:
The Freudian dream sequence in "The Doctor is Sin" had a fairly interesting backstory that had to be cut.
"Doctor Quymn, Medicine Woman" was slated to have a flashback implying that Dr. Quymn could be the boys' biological mother (hence why she resembles Dean so much) as well as some Pet the Dog moments for Dr. Venture.
A deleted scene on the season four vol disc would have shown Dr Killinger showing up to help The Revenge Society recapture some of that sweet, sweet evilness..
The post credits scene of "Bot Seeks Bot" shows that he actually did visit them, and has apparently been with them for a while offscreen, and his helping the Revenge Society plays a big part in "All This and Gargantua-2".