Chiana and Scorpius on Farscape were both intended to be guest characters, each for a single episode, Both instantly became main characters, with the latter replacing the main villain for the series. And then he did it again when they retconned Harvey into existence.

Babylon 5 has a few really good ones,* including a very early role for Bryan Cranston. But Wayne Alexander as the inquisitor is particularly notable. There's layers to the character and the performance really rises to meet the challenge. He perfectly balances a character that is cold, heartless and monstrous while having a surprising amount of humanity. In his performance you can see the idealist and the cynic, the zealot and the apathetic, cruel but without malice, a man who is totally devoted to his his mission who would like nothing more than to fail. His last line is understated and it should seem like an afterthought but it's only because of the performance and the writing that it can work so well because we're so invested in this character, and suddenly all the pieces fall into place.

* Walter Koenig as Bester needs to be mentioned but I believe he was always meant to be a recurring character.