Dawson Casting: Averted with most of the pre-teen/teenage cast members, the oldest of any of the Powell or Pembroke children in the series (in real life) was Nicole Eggert (born in 1972), who was never more than a year at the very least than her character Jamie.
Played straight with Scott Baio and Willie Aames, who were in their mid-20s (although, it is assumed that Charles and Buddy are supposed to be college freshmen in the first season); the year-and-a-half gap between seasons one and two left Baio and Aames still playing college students (presumably seniors, though the slowed timeline and the lack of mentions of their characters' advancement in school make this unclear) while they were right around 30 in the fifth and final season (both were born in 1960, the series ended in 1991).
Hey, It's That Guy!: Charles is Scott Baio, also known as ChaChi from Happy Days. Charles may be in charge, but The Fonz is in charge of Charles.
Buddy's sister Bunny in "The Buddy System" was Natalie.
Melanie (Jamie, Sarah and Adam's youngest cousin in the episode "Fair Exchange") later became Dorothy Jane Torkelson.
Ralph Malph won the lottery instead of Walter (thanks to Charles) in "It's a Blunderfull Life".
Wally Cleaver played Adam's music teacher who crashed their house party (and whom Sarah took in, mistakenly believing he was a homeless man, whom he looked a lot like) in "Summer Together, Fall Apart".
Well-known character actor Charles Nelson Reilly played the leader of a religious cult in "Cure for the Common Cult".
The Other Darrin: Jill Pembroke was originally played by Julie Cobb in the first season, however the role was recast with Lisa Donovan for the character's final appearance in the second season premiere "Amityville" (the first episode of the syndication run). It's odd when you consider that Michael Pearlman reprises his role as Jason Pembroke in that same episode.
Romance on the Set: By most reports, Scott Baio and Nicole Eggert dated towards the end of the show's run (by this point, Eggert was barely a legal adult, although not more than a year or two older than her character Jamie, who was still in high school in the final season).