There is no one simple answer to this. It all comes down to your strategy!

Sometimes it makes sense to target the enemy that is the biggest immediate threat to you. However, often it makes sense to target an enemy that you know you can kill on the next roll, and thereby reduce the total amount of active enemies, even if the eliminated enemy was not the biggest threat.

Then again, in many cases, it makes sense to target an enemy that is in front of (below) an enemy that is causing trouble to you, as you can then make the troublemaker fall. Falling stuns the enemy making it lose the rest of its turn.

You may also want to simply clear the way to reach a certain enemy in order to be able to hit it with your melee attacks.

TIP: You can target an enemy in the front row by tapping. The targeted enemy has a yellow square reticle around it.