After George's encounter with his alternate universe mother, the close-up of him slowly turning toward the camera in sheer frustration and terror is enough to send a chill up anyone's spine.
One of the most famous scenes is where Mary and George are together in Mary's house, which is a famously tense scene loaded with Belligerent Sexual Tension. The thing is, a lot of that tension was not scripted: Jimmy Stewart had served in World War II as a bomber pilot, and this was his first scene back from war. Apparently, his increasingly angry and passionate acting in that scene terrified both Donna Reed (playing Mary) and Frank Capra, the director.
Everything that happens to George in the alternate reality, really.
The scene when George stumbles into Pottersville is like an episode of The Twilight Zone. Could have inspired it, for all of that.
The scene where George comes home and yells at his wife and kids is frightening in a whole different way.
Everything during George's slow mental breakdown over the loss of the money is probably the movie's darkest point. Especially when he's officially been Driven to Suicide, the way he walks in the street and towards the bridge without noticing anything around him at all.
The deleted scene involving Clarence lecturing Mr. Potter and giving him a heart attack does sound pretty chilling, even if the villain is getting his comeuppance.
The look on George's face right before he jumps is rather unsettling.
The deleted scene explaining what happened to Martini the bartender in the alternate timeline. In the cemetery, George was going to find not only Martini's grave, but those of his wife and kids as well. They all burned to death when their terrible house in Potter's slum caught fire because George wasn't there to move them out. Reportedly, this was cut because it was deemed too depressing even for this sequence.
If you yourself are an "Uncle Billy", whether it's because you are learning-disabled, have had a TBI, or for any reason are chronically forgetful, what happens to him may be one of your worst nightmares.
Nick the bartender, Bert the policeman, and Ernie the taxi driver aren't the most major of characters and while their fates in Pottersville aren't as terrible as Gower's or Harry's, their transformations are still pretty scary. Nick bought out his boss, Mr. Martini, and is gleefully running the bar straight into the ground; Bert is a brutal cop who is implied to be in Potter's pocket; and Ernie has become a bitter cynic who has given up on life and been deserted by his family. It seems that not only was George singlehandedly holding the town's economy on his shoulders, he was also the only thing between several of his friends and total jerkassery.