The whole situation where Mr. Gower learned that his son has died. Even the ending where Mr. Gower physically punishes George for not doing his job only to learn that his grief misguided actions would have accidentally harmed someone. You can't help but cry throughout the whole ordeal.
After Mr. Gower realizes what he's done and how George saved him, he goes to hug George- and George cringes away, begging "Please don't hurt my sore ear again!" The look of absolute horror on Mr. Gower's face seeing that George is afraid of him is painful.
The scene where George comes home after learning that Uncle Billy had lost $8000 and takes out his frustration on his family is one of more massive tearjerkers in the movie, especially if you've been a kid who has been in a similar situation and thus can relate to George's children. Picture this, you're having a good time with your family without a care in the world. Suddenly, one or both your parents starts acting angry for reasons you probably can't understand. You don't know how to deal with it and anything you do will probably make them vent their rage towards you. Relationships get broken, personal belongings may get destroyed, and in worse cases, physical harm maybe inflicted upon you. You don't know why all this is happening and all you can do is cry.
Specifically after George has lost it, he orders his daughter Janey to start playing the piano again. She just sobs and says "oh Daddy"
Not to mention Mary's reaction when she starts to realize why George is acting the way he is. She gets this terrified look on her face as she starts calling up people for help. Meanwhile, the kids know something is wrong with their father, but no one knows exactly what.
George finding Harry's grave in the alternate timeline.
"Every man on that transport died. Harry wasn't there to save them because you weren't there to save Harry."
"Please! Please! I want to live again! I want to live again! I want to live again... please, God, let me live again..."
The way the angels describe the situation on Earth: