In the Steam PC version under Vista x64 with my NVidia GeForce 7600 videocard on a 1920x1200 screen, Strong Bad's eyes disappear from his mask sometimes. And Mazipan's eyes get replaced by a beige box occasionally.
And this display glitch: when flipping quickly from the map to past the secrets page to the awesomeness page, I end up with a display of the map page with the labels on the right side of secrets page superimposed on top of it, and the Awesomeness statistics not being rendered at all.
Once I sneaked from the plunger room into the Hall of Records as the Poopsmith had stopped shoveling, got hurled out by Strong Mad, then just after I landed outside the castle, the camera flicked over to the Poopsmith detecting me and sending Strong Mad "Footstep! Footstep! Footstep!". It was like it triggered both events at the same time but executed them in the wrong order. For a minute I walked around the lawn outside listening to Strong Mad's heavy footsteps tromping about inside.
During the end credits it said the Extended Play mode was unlocked, but when I started a new game, there wasn't any Extended Play option there, and the beginning of the game looked just the same. It's not clear where the Extended Play is.
They missed a joke opportunity when using the hedge clippers on Strong Sad's suicidal plant.