In the 70s version, Patrick O'Neal is the only one who holds the status of having played a guest killer *first* ("Blueprint For Murder") and then when he returned again it was in a "demoted" role ("Make Me A Perfect Murder"). This is in contrast to Robert Vaughn, who was serving the role of red herring when he appeared again.
Ray Milland of course graduated from important supporting role in "Death Lends A Hand" to killer in "The Greenhouse Jungle".
Hm I'd say Patrick Mc Goohan who only plays aa a murderer.
About Joyce van Patten (the murderer in "old fashioned murder", right?), she doesn't play only as a murderer, because in "Negative Reaction", she plays the religious sister who believes Columbo is a beggar.