These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Moral Event Horizon: West Dickens actually has the gallstones to hawk his All-Natural Snake Oil to the traumatized, grief-stricken, injured survivors of the Zombie Apocalypse, outright preying on their desperation, for the whopping price of 100 gold coins. John seems prepared to shoot West Dickens himself for such a low-class act, which scares him into at least giving the stuff away free.
Narm: The opening scenes where John's family is zombified lose a bit of punch due to the fact that John spends most of it in his underwear, which, while period accurate, looks a lot like footie pajamas. Seeing a stone cold badass like John Marston wearing that is more than a bit giggle-worthy, especially as the hog-tie animation puts his behind right in front of the camera. And the underwear is one of the available outfits for him, meaning you can have Marston take on the zombie apocalypse in his skivvies. Though given John's altogether nonchalant reactions to having to hogtie his wife and son and go off to stop the zombie apocalypse, it seems likely the whole scene was meant to be a little tongue-in-cheek to begin with.
That One Sidequest: There's one achievement that requires you to headshot 5 zombies in a row with the sniper rifle, without using Deadeye. It's ridiculously difficult to do this conventionally, because as soon as you pop the first one in a group, the rest will charge or stagger toward you with their heads bobbing all over the place, and the sniper rifle's aiming mechanic isn't the greatest. A better way to do it is to get into melee range with the sniper rifle equipped, and perform 5 executions.