In the 1988 film Who Framed Roger Rabbit one of the biggest problems was getting Roger (and the other cartoon characters) to look directly at Bob Hoskins and the other live action actors. Without clear believable eye direction, the characters didn't seem to be looking at each other, and the illusion failed.
You can see the memo on the left from animation director Richard Williams to the animation crew, reinforcing the importance of eye direction in sustaining the illusion that live action and animation were occupying the same visual space.
Since Who Framed Roger Rabbit I've worked on dozens of animated films. On every film it was important that the characters look at each other, and that the audience believes that the characters are looking at each other.