To really mess up big time, to fuck up with massively significant consequences.
On futurama, when Fry, pulled one of the lanterns from the old church, ruining Paul Revere's midnight ride; Professor Farnsworth informed him of his screwup of historical proportions by saying: "Fry, you dope! You've really screwed the granny this time.".
"Fry, you dope! You've really screwed the granny this time."
"You read from the Necronomicon and unleash Lord Cthulhu on Australia?! Well, it looks like you've really screwed the granny on this one."
v. From the t.v. show Futurama, to screw up, particularly to go back in time and mess up the future flow of events. From the episode where the main character, Fry, went back in time and slept with a woman who turned out to be his grandmother. Used in later episodes to indicate a time-related screw-up.
(After Fry took a lantern meant to signal Paul Revere) Fry, you've really screwed the granny this time!
Marty McFly, you kissed your mom?!? Boy, you've really screwed the granny this time!