Set your eyes on the prize because it's time to talk about how targeting works in LoR.
Targeting refers to a spell successfully taking effect. This means that it isn't just the act of casting the spell, but resolving it that matters. Confused? Let's grab the assist from everyone's favorite Prodigal Explorer, Ezreal.
Targeting the Enemy
Let's say you've set off 5 successful spells, with each of them striking true. You prepare to use a Mystic Shot on your opponent's unit. After all, Ezreal's level-up condition is that you (the player) have successfully targeted 6, or more, enemy units. However, setting off 6 successful spells is no easy task when a card like Deny exists.
Your opponent casts Deny on your Mystic Shot, and you have to watch as it fizzles out of existence. Oh well! At least your Ezreal leveled up, right?
Right! Even if Mystic Shot never gets to deal its damage to the enemy, targeting activates as soon as you play a card. So as soon as you played Mystic Shot from your hand, it counted as your sixth targeting spell, giving you just what you need to level up Ezreal! Huzzah!
Ezreal is all about targeting your enemies, but what if your card is the one that needs targeting to trigger an effect? Let's take a look at another of Piltover's treasure hunters, Jae Medarda.
Much like Ezreal, this treasure hunter's abilities depend on the success of spell-work, but this time your enemy has to successfully target Jae. This means if you really need to draw 1 card, you might want to let him take damage...just don't let him die!
Let's say your enemy casts Blade's Edge against Jae. He's a tough lad, so 1 damage won't be too devastating. You have a Deny in your hand, but it may be worth it to let the spell land, reducing his health to 5 and granting you a card. Who knows, there may be greater dangers worth Denying ahead!
Now, what if your enemy casts Thermogenic Beam to deal a whopping 6 damage to Jae? He can't very well grant you a card if he's been obliterated off the board. This is when that Deny would be handy! Since targeting activates when a card is played, you can Deny the damage from Thermogenic Beam and still reap the benefits of Jae's ability and draw a card.
Remember - effects from Targeting only succeed if the card in question survives the encounter!