It is a study of different forms of loneliness, and the bleakness and sadness resonate with readers. There is a universality in the portrayal of these characters.
For example, Crooks is a negro living in a white society. Not only is he lonely because the lives of the workers were shifting and impermanent, but also because of racism and unkindness with which he is unjustifiably treated. It is also psychologically accurate; think about Crooks' reactions in the chapter which focuses on him. He longs for company and cautiously invites people into his room, while his anger and hurt make him want to reject visitors. This dual process reflects the inner conflict that humans often battle with.
Curley's wife might be said to represent downtrodden women, treated as negligible. ('Ain't she a lulu'?). She is not even given a name. She handles every situation clumsily and, when feeling insulted, lashes out at the person who is yet lower in the hierarchy. ('I could get you strung up'). Yet, her life is wretched, and she is dehumanised by the treatment she has received all her life.
Look at each character from the point of view of their loneliness. They reflect the sadness of human existence.
There are many reasons why Steinbeck's work is so popular. One reason why this is might be due to the fact that it is so powerful, yet so compellingly short. It seems like Steinbeck maximizes each word, each scene, and each moment to explore the nature of human beings, their dreams and hopes, as well as the crushing forces of their world. His exploration of such powerful elements is done in a manner that is not redundant or containing "extra writing." The novel is short and powerful, making it well received by both students and readers, alike. Contributing to its popularity is the universal feel of its characters. Lenny's childlike approach to life as well as his hopes can be appreciated by anyone. George's desire to "make it big," or skip work to go to a ballgame, and envision a life which is so hopeful and different from what it is proves to be very compelling. Even antagonists like Curley can be appreciated by many, as the notion of an angry and resentful character who is empowered with wealth and status is a relevant notion (Given the fact he is also tiny allows many to identify with his "Napoleon"- like syndrome.) Finally, Steinbeck's novel might be so popular because it shows the difficulty of economic conditions on the human psyche. As economic difficulties become something that is more understood on a wider level, examining this theme through Steinbeck's eyes creates a very compelling portrait, allowing one to understand the role of material contingency on the hopes and dreams of individuals. There is a sad empathy and yet feeling of hollowness that results in seeing George have to kill Lenny and seek the abandonment of dreams in favor of the reality that guides him. Steinbeck's picture of what is and how what can be is sacrificed on its altar is very powerful to many readers and thinkers. The ideas of "the American Dream" and opportunity ideology are seen in a new light thanks to Steinbeck's novel, contributing to its popularity.