I think that Steinbeck's construction of so many lonely characters helps to bring out how special the relationship between George and Lennie actually is. On one hand, the relationship is so significance precisely because in a world where there are so many lonely people, two people have found the loyalty to stand by one another. Another reason why the loneliness present in the outside world is significant is because George and Lennie have found a way to be fundamentally different than the world around them, transcending what is into what should be. I think that Steinbeck's inclusion of so many people who are lonely also helps to illuminate the despair and agonizing isolation brought on by the Great Depression and intrinsic to the plight of the migrant worker. Steinbeck is socially astute enough to suggest that while there is an economic reality being deprived in such a condition, its real pain is the emotional severance of bonds or connections to other human beings. In this respect, Steinbeck's depiction of so many lonely people helps to illuminate how the aspect of isolation and despair is something that human beings must actively resist, preventing themselves from becoming like the hopelessness and loneliness found in the characters that work and live on the ranch.
By using so many lonely characters in Of Mice and Men, Steinbeck reflects life of real migrant workers during the period following the Great Depression and during the Dust Bowl. Many people went to search for employment out west, such as in California, the setting of many of Steinbeck's novels. Drought and poor farming techniques had led to much of the lack of available work and people were in search of ways to survive. The migrants set up "camps" wherever they could and would search for work in the local area until there was none. Then, they would move on to another location to begin a new search. Because of this frequent movement, few people had ties to others. Relationships could not be very meaningful because those with whom one worked were also in the same habit of picking up and moving at a minute's notice. The motivation for these frequent moves and short periods of employment at one farm was survival. As a result, loneliness is an appropriate theme for the novel considering the context. Steinbeck's reflection of the theme in Curley's wife, George and Lennie, Candy, Crooks, Slim, etc. merely mirrors Americans during this time.