Loneliness is a key theme. All of the men on the ranch are lonely as in the 1930s ranchhands would have drifted around from ranch to ranch on their own. The great depression shook the country to the core and left people desperate and lonely.
Lennie and George are different because they are not lonely. They have each other to rely on. 'I got you and you got me'. The irony of this is that George can sometimes not appreciate Lennie being there with him because it's so hard to have to care for someone who cannot care for themselves. 'When I think of the swell time I could have without you' George says in the midst of anger. We know that he sticks with Lennie because he promised Aunt Clara he'd look after him. He also feels guilty for the time he told Lennie to jump into the river when he almost drowned.
Dreams are another key theme. One of the first things we learn about Lennie and George is that they have a dream to own their own house and 'live off the fatta' the land'. This is called the American dream, and was not uncommon. As Crooks says, …