I wonder whether one theme we can use to link these two excellent stories is actually that of the way characters in both texts are forced to confront their various idealistic illusions about life and have to accept the brutal facts of reality by the end of both stories.
Let us consider the grandmother and also the Misfit in "A Good Man is Hard to Find." To the reader, it is clear that the grandmother lives in a world where she casts herself as a wronged woman. She deliberately chooses her clothes thinking about how she wants to be viewed if she dies in a car accident and is blind to her own selfishness and manipulation with her family. The Misfit, too, considers life is all about having a good time by doing what you want to do and killing others for personal pleasure. By the end of the story, both have changed. When the grandmother says to the Misfit, "You're one of my children!" she is implicitly recognising that both she and the Misfit are sinful humans, and she is able to see herself for who she is. The Misfit, too, at the end of the story, contradicts his earlier statement, now saying there is no "fun" in killing.
In Of Mice and Men, George and Lennie have a dream that acts almost as a refrain as they imagine managing to buy some land and then "livin' of the fatta' the land." This dream sustains them and keeps them going while they are facing such hardship and pressure that threatens to destroy their friendship. By the end of the story, however, George is forced to realise that such a dream can never become reality thanks to the massive social and political forces that are opposed against them, and his dream dies when he places a bullet in the back of Lennie's neck.
In both stories, therefore, reality is a force that strips characters of their own illusions and pretensions and forces them to see themselves and their world in a more realistic, if not more depressing, fashion.