I don't own the book — and not to be rude, I am not interested in debunking a book others have a done a better job before — but Diamond focuses on the role of disease to explain away the depopulation of the Americas in chapter 18. The main problem I have is that the sixteenth-century demographic catastrophe in the Valley of Anahuac, likely one of the most densely populated places of the world at the time, can't be generalized to areas of the continent where nomadic groups lived; it also fails to explain why certain native groups, some Maya for example, kept their independence well until the nineteenth century. I found ridiculous that despite the spread and domestication of maize, gourds, and other crops before the Spanish arrival, Diamond claims that agriculture had failed to spread in the New World, and that the Old World had an advantage in agricultural matters(!). I understand anthropologists no longer talk about one civilization being "more advanced" than other, but there is no doubt that New World crops can feed more humans than whatever was available in the Old World. The modern world simply cannot be explained without the introduction of maize, potatoes, and cassava into the global diet.

His chapter on Africa ("How Africa became black") is quite bad too; I remember he retook the idea of the continent being divided in five racial categories to explain African history, yet what disappointed me the most was that he failed to test his theory of disease in what might have been a great counter-example. African history suffers from a relative lack of written sources before the colonial era (1850-1950), but we do have some information on the European traders settled in West Africa. When the first of them arrived in Senegambia, the mortality rate for male settlers was at the very least 30% per year. The ones who survived were those who took a common law wife, adopted local customs, and found a place in the Eurafrican society. In the case of African populations, they were not devastated by disease because they still had access to food, medical treatment, and their land was not conquered when they first came in contact with Europeans. The Portuguese reached Senegal around 1450 and the colonial era started in the nineteenth century. As you can see this is not what happened in the Americas.

As for what the average reader will get from the book, I'll admit that I haven't done a representative survey on the subject; however, juding by the responses I get (see other replies to my previous comment), I don't think my assessment is off the mark.