Although many of the killers were played by outstanding actors (Jack Cassidy, Robert Culp
and Clive Reville being among my favorites),
the best combination of actor along with outstanding plot
(with premeditated murders being better than
sponataneous ones) were Robert Vaughn ("Troubled
Waters") and Dick van **** ("Negative Reaction").
I might add Lee Grant ("Ransom for a Dead Man")
although her performance was not quite up to those of the other two. These arrogant killers are all totally cold-blooded assassins.

There were many performances ranging from good to absolutely superb in the villainous characterisation department.

For me Jack Cassidy's characters had that quintessential smugness and self-satisfication that set him apart from the others (however he did get three tries at the villain!).

If you look at the one-offs, I thought Oskar Werner was remarkably cold (without even trying) in "Playback". Leonard Nimoy was also superbly cold in "Stitch in Crime."

Perhaps the most underestimated/underrated performance was from Laurence Harvey, whose initial jitteriness dissipates into ruthless and calculating behaviour, in "The Most Dangerous Match."

To answer the original question my favorite would be Robert Culp. He was great in Double Exposure(my favorite)and Death Lands A Hand. He did what he could in the Most Crucial Game which was a weaker episode.
Jack Cassidy is good but I don't know he seems to just be playing Jack Cassidy sometimes. Two of his roles are almost identical(Murder by the Book & Publish or Perish) but Now You See Him was his best to me. He did a good job in that. He's the 2nd best of the three.
Patrick McGoohan is good but hes a bit eccentric to me. He was very good in By Dawns Early Light (emmy nomination) but I didn't like him in Identity Crisis too much.(a bit weird)3rd.

Some other favorite villians of mine would be: Roddy McDowall, William Shatner, Ricardo Montalban, John Cassavetes,Trish Van Devere(favorite female) ,Donald Pleasance,Clive Revill, Martin Landau, & Robert Vaughn.