Before I answer, I wanna point out that the couples in live action shows are also not real. Superman played by Henry Cavill is equally fictional.

Humans are hard wired to sympathise with things. If you call a pencil “Tony” and someone snaps it in half, you feel bad for the pencil. It’s just the way we work. If you feel bad for a fictional couple, that means the creators have done their job correctly.

What is this thing you humans call… empathy?

I think this response is just a natural demonstration of empathy. not a bad thing, if you ask me!

Empathy is a completely natural instinct. Ever heard the phrase “humans will pack bond with everything”? People see another creature in distress and automatically feel bad for it and want to help, even when those are wild animals and potentially dangerous. Sometimes that instinct can even be triggered by plants or objects - a dried out flower with hanging petals looks “sad” to us even tho noone has ever proven that flowers are capable of such emotions. A stuck roomba trying to get itself unstuck looks as if it is struggling even if it just runs a pre-programmed set of motions. Yet most humans with a basic level of empathy look at these and immediatly think “oh no, poor thing!”

Whether or not the recipient of your empathetic feelings is real, or able to feel, that question is an afterthought. It is something that happens after your instinct has been triggered already.

… or should be, IMHO. I do not trust anyone who is able to somehow override that instinct and first ask whether or not the struggling creature/person “deserves” empathy, based on whatever criteria they deem worthy …

I only knew the wife in Up for 5 minutes and she had me bawling like a baby.

Cartoons wouldn’t even work for storytelling if you didn’t form empathy for the characters.

To paraphrase Roger Ebert in his Grave of the Fireflies essay, in live action you feel for the person on camera. In animation it’s the idea or concept that affects you, which is much more emotional.

You feel an emotion based on the context. Be it in a live action movie, anime, pictures or even less visual with plain text.

My two cents; I think it’s because you get lost in the story for even a brief time. And all stories are built out of human experiences and emotions. They are made to get some sense of distraction, or relief, or joy, or to change your views, or whatever the goal might be. Cartoons are no different.
Any story aims to get you involved; if you wouldn’t get the feeling of ‘being in the story’, you would not find it interesting and would look for something else.

Depends on the story and how good the characters are setup.