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."