It doesn't necessarily have to be a Grey Cup game, you could also define significant as important, too, but what are some that come to mind. I'll start with one, and people can add as they wish:

Arland Bruce III kick-return touchdown in the 2004 Eastern Final. The Argos had lost two straight Eastern Finals to the Alouettes, and Montreal had just taken a 7-0 lead. Bruce's kick-return TD in response helped Toronto keep pace, and while it was a lower-scoring game, the Argos eventually came on top 26-18.