People view Lennie as a misfit for several reasons. First he is immense. His size and power alone set him apart. However, he is obviously mentally challenged. So this too sets him apart.
While George cares for him, he nevertheless is often frustrated by being weighted down by this \'misfit.\' Remember Lennie has gotten them into trouble before. They can never seem to settle down long before Lennie does something that causes them to have to pack up and hit the road again.
Curly\'s wife sees Lennie as childlike, yet he is obviously a stout man. But he is unlike the other men on the farm. He listens to her and seems to have very gentle way about him. This too contrasts most of the other men on the farm.
However, it is Lennie\'s size and mental deficiencies that lead to his demise. He is really his own worst enemy. Despite George\'s warnings to leave things alone and to stop keeping dead mice as \'pets,\' Lennie cannot bring himself to do it. Nor can he keep himself from what he does to Curly\'s wife at the novels climax.
I have always thought of Lennie like a wild animal that has been tamed or taken into captivity. They may seem like great companions, but there remains that sense of danger about them that they could go back to their wild ways at any moment. Lennie, despite being innocent and naive, has all of that raw power at his disposal. And it brings about his demise.