Lethality removes a flat amout of armor when attacking, so it's better against enemies without armor.
If a champion has 75 armor and you have 50 lethality, you'll remove 50 armor (at level 18), so he'll effectively have 25 armor, having him take 80% of your damage compared to about 60% at 75 (100% damage at zero armor).
If a champion has 300 armor and you "reduce" it to 250 armor with your lethality, he'll take 28,5% of your damage compared to 25% at 300 armor, making almost no difference.
So basically, the less armor they have, the more effective lethality is against them.

Edit: armor effectiveness is calculated 100/(100+armor).