Seth MacFarlane's collection of zany animated sitcoms shares many common elements, one being the huge entourage of both major and minor characters unique to each show. Like its peers, Family Guy and The Cleveland Show, American Dad! has its own roster of varied and wildly entertaining characters that can pop in and out of the Smiths' lives at any time.
But for a certain few of these, their first appearance in the town of Langley Falls is also their last. In some cases it's justified, that character having served their purpose with no reason to stick around afterwards; in others, we're given only a glimpse of what they have to offer, yet somehow, they've never reemerged from whatever hole they crawled into after their fifteen minutes of fame.
Either way, both groups represent the true one-hit wonders of American Dad! - those who graced viewers with their presence for less than 20 minutes, but still managed to leave a lasting impression on the show and its followers alike.
It's important to note that this list won't include any of Roger's personas, as, completely unique though they may be, they're all still Roger at the end of the day. In addition, fleeting background cameos do not count - only prominent roles that actively affect the plot of the episode.