How can multiple players have unique playlist under one application?

You can create multiple signs under an application and assign each sign to a player. To create a new sign, check the box to the left of Enable Multiple Signs, then click on New Sign at the upper rigth next to Player Preview. See image.

Here in the image, we  named signs as tv1, tv2 and tv3. You program slots at Application level. For each sign, click on the zone you want to change playlist, deselect the slots you do not want to play. Now you have unique playlist for each sign/player.