When you're fighting a world boss, significant champion, or any enemy that is an event unto itself (read: has an event with a skull symbol, and is the main target of the event), you can click on its orange health bar in the sidebar to target that enemy.

This can be very useful in chaotic fights with lots of mobs running around, when hitting tab might guess wrong a dozen times before putting you back on the main one, and there's too much visual clutter to get a good targeting click on the mob itself.