This answer is definitely going to depend on who you ask. Please don't take my response as representative of all readers of this novel.
I didn't like it. Not only is it about characters struggling through the Great Depression, it is also flat out depressing to read. The characters may talk about having hope, but the reader knows throughout the story that Lennie and George are not going to escape their lot in life. They are perpetual victims within their present situation and society. Add to that the end of the novel where George kills Lennie, and you have a very dark and depressing novel. I know it is representative of the period and genre, which I have never particularly enjoyed.
I also feel that the novel portrays women in a very negative light. This is easily illustrated by the lack of women in the novel. Curley's wife is the only female character, and she doesn't even get a name. I might be okay with that if she was a "good" character, but she isn't. She is manipulative and promiscuous and even tries to seduce Lennie. I'm sure that I am in the minority of readers regarding my opinion of the novel, but that's what makes literature so fun to discuss.