Part of the reason why the characters feel isolated all the time in Steinbeck's work is that they carry the death of their own dreams. This weight is a heavy burden to carry, and is one that facilitates a sense of isolation. For example, Curley's wife's dream of being in "pitchers" was denied to her. Her entire being on the farm, as realized towards the end of the narrative, is one in which she continually thinks back to what might have been, to what could have been. This is the reason she finds it difficult to connect with people. For a moment, she is able to overcome this when she finds a willing audience in Lennie, something that ends up leading to her own negation in the process.
Crooks is isolated for the same reason. Being a man of color in a White person's world, Crooks is able to recognize that at one point in time, he had a dream of companionship. At one point in time in his life, he and his family owned property and shared in the experience as a unit. This sense of togetherness is the opposite of the isolation and alienation he experiences now. In his own death of a dream of companionship, he, too, is alone. This sense of alienation is what causes Candy to be alone, also. He quickly seeks to overcome this in partaking in George's and Lennie's dream. For a moment, he is able to overcome his isolation. Yet, when he encounters the body of Curley's wife, Candy understands that he cannot escape the sense of isolation that will follow him, something that he is doomed to face alone after not speaking up for his dog at the most critical of moments.
There is isolation around the ranch because of this death of dreams. Yet, George and Lennie are different. As if on cue, the reason they are different is because they have one another. Steinbeck might be deliberately suggesting that individuals can overcome their own isolation and their own hurt if they recognize that they are not alone. George and Lennie experience the death of their own dreams, but it does not stop them from envisioning future dreams because they have one another. The isolation that is felt on the farm is not something that George and Lennie feel because "I got you and you got me." It is a refrain that is heard at the start of the narrative, in its middle, and at the end.