A Protestant I was speaking with brought up Genesis 22 as an example of Penal Substitution, where instead of Abraham sacrificing his son Isaac, a ram was sacrificed instead. I was shocked that he would use this as an example, for there are some pretty serious errors in that argument. Then I realized this is a great proof against the doctrine of Penal Substitution, so I decided to share my thoughts.
First of all, Abraham was already justified by the time Genesis 22 came around, so to suggest Abraham had to atone for his sins despite being justified is a blatant contradiction in Protestant theology. In fact, Protestants are adamant that James 2:21-24 (talking about Genesis 22:13) is speaking of Abraham's vindication, not his justification, so the sacrifice couldn't have been of a PSub nature. Second of all, this argument suggests that Isaac could act as a substitute for Abraham's sins in the first place, which is impossible because Isaac was a sinner himself (and Sacrifices must be pure).
So if this situation was not that of Penal Substitution, then this means Sacrifices involving animals can be done for other reasons, such as showing thanksgiving to God. This refutes the idea that just because an animal is slain that it must be taking someone's punishment. And since this famous OT example prefigured the Father sending the Son to be a sacrifice, then this powerful foreshadowing points away from Jesus being a Penal Substitute as well.