There's something intrinsically funny about that word. I think part of it is that it sounds like of like "masturbation", and part of it is that it's so unusually specific - why do we need a word for throwing someone out a window?
I think the answer about why it’s so specific is if you just say you threw someone out of a window people might assume it was only one story high and not lethal. Defenestration tells you that it was a high window, and often implies the ejection of the owner or a legitimate occupant. Similar to shock vs electrocution.
Even if (this is a challenge for the average English speaker like myself) you maintain in your conscious mind "fenestra = window", I think it's still so funny, because it sounds like you're removing the window from the person (a la decapitation).
