Static people and animals should be looking into positive space as well. The classic image of somebody pointing and looking should always be into this larger area ahead of them, if only because it looks strange for people to be pointing out of the frame, away from the great space that we, the viewer, can see behind them. We see examples of this all the time on television, when an out-of-shot interviewer is talking to a guest. The person will be talking directly to the interviewer, but from left or right of the frame (again the Rule of Thirds), and looking into the larger space.
Of course all rules can be broken and powerful stories or scenarios can be told by having a subject leaving the frame (moving into negative space). For example, if there is a person walking out of frame, while behind them in the larger space is a sign saying “Beware of Landmines”.