Crybaby Clown also seems like an allusion to Hamill's role as Macendale/Hobgoblin on Spider-Man: The Animated Series, since the villain is more practical-minded than Joker, and both are shallow pretty-boys who romance the local rich girl who is fed up with her distracted ex/potential beau and turn to destructive crime waves in the name of money/fame. Both Daphne and Felicia Hardy are made to feel like fools when their date is unmasked.
Early on in season two, Velma seems to have become pretty good friends with Hot Dog Water. It probably doesn't hurt Hot Dog Water's voice actress Linda Cardellini has a bit of a past relationshipwith Velma...
In Episode 12, Harlan Ellison spouts out a paragraph about the monster, full of "f" words (but not theF Word).
Tim Matheson is basically voicing an adult version of Jonny Quest, to the point where the character in season two is radically redesigned from his teenage self to resemble Jonny.
Gary Cole becoming Fred's adopted father isn't the first time he's taken a job from Tim Matheson. He also became Vice President in The West Wing after Matheson's character John Hoynes had to resign in disgrace.
For the Freak of Crystal Cove, Frank Welker uses the voice he used for the Boogieman. Whether by design or coincidence, the Freak has a few visual similarities to Boogie (such as being pale white and having horns).
Paul Rugg voiced a professor character in an episode he wrote.
Doing It for the Art: The reason Baylor Hotner initially became Crybaby Clown, to do research for his next film.
Fandom Nod: In "Dance Of The Undead", when asked why the Hex Girls went back to their original outfits (resembling the ones worn in Witch's Ghost), they say that fans just preferred their original look. Some fans complained about their new look, so this is more than likely a little in-joke.
Fan Nickname: The Nibiru Entity is actually referred to as The Evil Entity in the series proper.
Jossed: Many people liked to believe that Cassidy survived the underwater explosion, and that she was just hiding. This is not the case, as she does not reappear until the timeline had been reset.
Casey Kasem retired from the role of Shaggy, and handed the role over to Matthew Lillard. This is also a role reprisal from the theatrical live action films.
Lewis Black voices Mr. E, but one episode has him voiced by Jeff Bennett.
Due to Vincent Price's death, Maurice La Marche voices Vincent Van Ghoul.
Gary, Ethan's friend, was voiced by Tony Cervone in season 1 and by Jeff Bennett in season 2.
Screwed by the Network: Despite universal praise the series was screwed in Season 2 where there would often be months between new episodes and no news of when new episodes would come out. It was easier to find the episodes online rather than TV. Luckily however, they managed to wrap up the series at the end instead of outright canceling it like many other shows that have been screwed.