A particularly bizarre example occurred with Matt Lanter (Brody the rapist quarterback), who had previously been a regular on Commander In Chief, playing the President's teenage son. The weird part is that Hayden Panettiere had a guest role on Commander In Chief, and the two of them ended up making out. Hopefully, their prior... familiarity... made filming the rape scene a little easier.
The obvious example is how volume 3 was cut short, with plot threads obvious to be related to the main story ending up going nowhere. A bigger example would be the entire style of the series: The original intent was to have a revolving cast, with most characters not returning in future seasons. What could have been, indeed, if after season 2 we didn't have to deal with most of the extended Petrelli family?
The Aborted Arcs caused by the writer's strike, which led to the Seasonal Rot which the series never fully recovered from.
The Season 2 DVD had an Alternate Ending in which Peter failed to catch the virus vial that Adam had dropped. It was planned that the virus would have been unleashed, and the latter half of the season would have been dedicated to finding a cure with Maya performing a Heroic Sacrifice by using her plague power to absorb the virus, killing her in the process.
The writers were originally going to have a Kill 'em All ending at the end of season 1 and have a rotating cast each season. They didn't anticipate the characters becoming popular and developing a fanbase or Executive Meddling and it became increasingly difficult to properly use the Super Power Lottery winners like Peter and Hiro again.
Elle was supposed to show up in the "I Am Become Death" future as the mother of the little boy, but conflicts with Kristen Bell's filming schedule forced the writers to cut the Sylar/Elle arc short and kill her off.
Tim Sale is the artist behind most of the art featured on the show, except for Sylar's art, which was done by Alex Maleev, Peter's first stick figure doodle (done by Jeph Loeb), and Molly's doodles, which the actress did herself. Sale and Jeph Loeb are frequent comics collaborators, which strengthened the show's ties to comics.
The vignettes that aired promoting new characters that would debut in the following season is a technique that originated in Professional Wrestling, specifically in Memphis, TN with The Fabulous Ones in the early 1980s and is still used today.