This book was written at a time of great turmoil in America. Not only was World War II just ending, this was also during the civil rights movement, around the exact time that Brown vs Board of Education was passed, undoing the doctrine of "separate but equal." Some White-Americans at the time, were afraid that their way of life was being undone, much the way that Neville's life had been undone by the vampires.
The vampires in I Am Legend are a plague. They have caught the unsuspecting humans off guard and threaten everything they know and believe in. The fear of their takeover is similar to the fear that Anglo-Americans might have had in the 50s-60s about African-Americans taking over. The vampires are inherently evil and different, a race that must be stamped out or contained.
Patterson talks about the "half breed" in this novel, which definitely mirrors a lot of western ideas about race. There is lots of fear associated with the half breed. Fear that they will assimilate into society unbeknownst to the masses, forever changing what that "mass" is. After Reconstruction, the idea of a half breed was introduced. It was decided that only people who had 1/8 of African ancestry could still be considered white. This rule was strictly enforced, so that no one might escape it and be considered white when they were not (in the eyes of the law).
White blood was considered to be pure blood and whites did not want their race to be "dirtied" with the blood of a different ethnicity. That is why half breeds were looked down upon, they were neither one ethnicity nor the other, they were a group all to themselves.
Neville sees himself as "normal" and the vampires as defected. We can see this when he is talking to Ruth and says "You're on trial, not me." He is insinuating that she and all the others must be judged against him, the "normal" one.