The abstract of the paper Set Theory for Category Theory (arXiv:0810.1279 [math.CT]) by Michael Shulman opens thus:
Questions of set-theoretic size play an essential role in category theory, especially the distinction between sets and proper classes (or small sets and large sets). There are many different ways to formalize this, and which choice is made can have noticeable effects on what categorical constructions are permissible.
It appears to me that these issues arise when category theory is formalized within the context of some set theory, but as far as I know it is also possible to take category theory itself as the foundation of mathematics, with no reference to any underlying set theory. If this approach is taken, is there any good reason to distinguishing between small sets and large sets, and between small and large categories?
Forget about good reason, is there even any sense in distinguishing between small and large categories if category theory is taken as the foundation of mathematics? Take, for instance, the following definition of small and large categories from Wikipedia:
A category C is called small if both ob(C) and hom(C) are actually sets and not proper classes, and large otherwise.
If there is no underlying set theory in which category theory is formulated, does this definition even make sense? And even if you can somehow imbue it with sense, is it worthwhile to do so?
Category theory wants to contain set theory (Set is an important category! Also, sets are basically discrete categories), so all of the usual reasons compel you to pay attention to size issues. They can even show up without appealing to sets; e.g. there can't be a category of all categories.
A more category-theoretic flavoring of size issues is:
so even if there weren't size issues, smallness would still be an important topic in category theory, even if it were just a special case of enriched category theory and internal category theory.