I've been thinking that the 13th Man penalty is the worst, costliest penalty ever. Here's why.
1) While all penalties are bad, some are incurred while trying to help your team. e.g. pass interference, holding, no yards, intentional grounding. In each case, the offending player was most likely trying to get away with something in the name of improving his team's chances on the play.
Other penalties are selfish or negligent and cannot be argued to be an attempt to help your team, because even if you get away with it the team is no better off. e.g. unsportsmanlike conduct, illegal substitution.
2) While many penalties are costly, it is rare that you can say unequivocally that a particular penalty absolutely made the difference between winning and losing. If it's not on the last play of the game, there is always a theoretical chance for your team to win on the next play.
e.g. You extend the other team's winning drive with a roughing the passer call on a third down incompletion -- costly, but your defence still has a chance to stop them.
e.g. Your holding penalty negates your team's winning TD pass -- they still get another down.
In this year's Grey Cup, without question the game would have ended were it not for the penalty. And the ensuing FG from 33 yards is next to impossible to stop.
3) There's only one Grey Cup each year. No matter what you do in any other game, the stakes can never be as high as in the championship game.
In other words, by my reasoning, to find a penalty as costly as the one in question, you would need to think of another Grey Cup game where a last-second, selfish or negligent penalty unarguably made the difference between winning and losing.
I'm not sure if there has been such an event in league history. But even in the unlikely event that there has been, the 13th Man penalty would still be tied for Worst Ever.