This game has a very distinct artstyle that has lot of disturbing content and imagery done in a cartoony way so that it is bearable
Experienced Isaac players usually forget about what they're looking at and just see it as numbers and mechanics, so this page is a reminder of what you're ACTUALLY looking at.
And a great place to start would be
ITEM DESIGN
Almost every items gives a positive effect, but that doesn't mean the items are "good", but that they're what the game thinks its good.
The best place where you can see that is in the main boss pool items that give you an hp up.
They are a poop in a bowl, wet dog food in a can, try dog food, rancid milk, rotten meat with a key in it, a can with that I think its cat food, a dog treat and moldy bread.
All those items are named, "Lunch", "Dinner" , "Dessert", "Breakfast", "Rotten meat", "Supper", "A Snack" and "Midnight Snack" respectively.
During the game and the choice of names that are given for certain items makes you think that those are the names Isaac (the 5 year old you play as) gave them which also reflects on how much of a great life Isaac has,
or,
if the theory of "its all in his head and his drawings" that the game gives you is right, it shows you how imaginative Isaac is.
Another way of seeing the game's art direction is seeing how some items affect Isaac's appearence.
With most of Isaac's accessory changes that give him positive stat increases or abilities, visibly either harm Isaac, traumatize him, give him deseases or are references of the creator's previous projects,
all of which work very well with the fact that Isaac fights with his tears
