Monday, 26th January 2015, 20:54 by and into
Zot is very consistent at being the most dangerous area in the game, and also incidentally the only area in the game in which you have a good chance at being in a situation where you cannot avoid picking up a mutation or three. (EDIT: Certain things can happen in Pan or in Hell that are unfair in a way that Zot is not unfair, IMO, but on the whole, even in my 15 rune games across many different characters, Zot tends to be more dangerous than "extended," despite saving Zot until the end.)
You are, strictly speaking, lowering your win chances by doing any "optional" content beyond what you gotta do to win, but if you like that optional content then by all means complete the Hells, Pan, etc., whatever you like. However, if you are going to extend the length of your game beyond 3 runes, then you really should do Zot last.