EC2 pays off most when usage patterns vary widely. Animation render farms is a good case. Do no rendering today, fire up 100 computers tomorrow to knock off a few scenes.
I'm still waiting for the massively parallel key cracking kit to show up. Need to crack a key fast? Fire up 500 computers for an hour.
Also good for on-demand overload. If you've written a custom load balancer (like I'm doing via mod_rewrite script), you can fob off unexpected load to some EC2 machines on the fly. Useful if you run a site that occasionally gets slashdotted/dugg/reddited.