Arthas needs a victory.
Ever since the Battle at Light's Hope Chapel, Arthas has lost battle after battle. The players enter Northrend, and from zone to zone, they defeat Arthas at every turn. The closest he comes to victory is at the Wrathgate, but the Forsaken interfere and he has to retreat. Even in the latest patch, he's all, "Fools, now you face Anub'arak", and then the players promptly kill Anub'arak. Again.
As a result, Arthas is coming off as a "paper tiger". He shows up, makes a speech, and retreats defeated. A good villain needs to be respected. In a normal story, the heroes can't go from victory to victory. They need to suffer setbacks. For example, The Empire Strikes Back is one long acknowledgement of this necessity.
But in an RPG, can the game really impose failure on the players? To me, a game putting you into a no-win situation seems very unfair. In some ways, this is because we already have failure in the game, but it's just a temporary state. You wipe, and you try again. Victory may be hard, but it is possible. The game forcing you to lose seems like a betrayal of this principle.
But for the good of the storyline, Arthas needs a victory to reinstate him as a real threat.
I don't think that Arthas can score a victory over the players directly without it coming across as contrived.1 The best path is probably to kill at least one major NPC in combat at the start of patch 3.3.
I think there are three candidates that would immediately restore Arthas' credentials as a villain: Jaina Proudmoore, High Overlord Saurfang, or Tirion Fordring. Of these three, Tirion is probably the best choice, as the central opponent of Arthas. As an additional effect, Arthas could shatter the Ashbringer, bringing tears to the eyes of all warriors, paladins, and death knights.
Jaina and Saurfang are also good choices because they tend to be popular with their respective factions. The downside here is that a death would have less impact on the opposing faction.
1 Though it would be hilarious if Arthas killed your little Argent Crusade squire. It would be pretty hardcore to permanently lose a pet. By WoW standards, anyways.