The destruction of Cybertron, the heroes' Robot Buddy in "The Deadly Pyramid". He was supposed to get better, but they never got around to it.
The scientist said it could take years to fix him.
Also, the fact that this show may never get a revival. An interview with Lance Falk (an artist and writer for the series) confirmed that the chances of it are "zero to less than zero". DVDs are now available, albeit not remastered. Then again, Japan has made anime of The Powerpuff Girls and Lilo & Stitch, so someday there might be an anime for this too.