The first up on my reading of the 306 greatest books is Of Mice and Men by John Steinbeck. This book can be found on the Sybervision, BBC, and My Book Lists.
While I had read this book in high school and I consider this the first book I have read on my list, I have since gone back and reread it. And my, what a depressing story this is. It has a very strong Great Depression vibe to it as well, although the Great Depression is never mentioned in the story. The plot follows two companions, one of which would be considered to have a learning disability today, Lennie, while the other individual, George, is the one that takes care of him and tries to make sure he doesn't get into trouble. Which doesn't always work out the way that he hopes. While the story is very short and follows only one instance of them as traveling farm hands to a new farm, the story itself delves into racism, ableism at the time, and in some instances men's mental health. It is a profound reading experience coming at it from a 21st century mind frame. I don't think I got anywhere near all those details in high school and this is one I was happy to travel back to. A must read in my opinion.