I have been doing a Insanity difficulty playthrough in Mass Effect 3. In Insanity monsters hit harder, move faster, and have a lot more health. It is certainly challenging but I think I managed to hit the overpowered strategy by playing a Adept specialized in Biotic Explosions. I really like the Biotic Explosions mechanic where you combine different kinds of Biotic powers to create big detonations because it creates all kinds of interesting choices in terms of what powers you use, what order you use them in, and how you spec your character. It feels like a very different and very interesting version of the game when compared to the more straightforward Soldier who just shoots people in the head with a sniper rifle over and over.
The problem is that Biotic Explosions have a really bizarre damage mechanic. Unlike everything else in the game like guns and regular biotic or tech attacks Biotic Explosions base their damage on enemy health totals. A gunshot or a Incinerate might do 200 damage so it would take 3 attacks to kill a monster on Normal difficulty or 6 attacks to kill the same monster on Insanity. Biotic Explosions scale with health though, so if you can kill an enemy with two Biotic Explosions in Normal the same holds through on all difficulty levels.
Scaling damage to enemy health levels just isn't a good idea. In Diablo 2 it was just as problematic when Necromancers used Corpse Explosion to do 60% of a monster's health to all nearby enemies. It really doesn't make sense to scale things this way when a big part of difficulty scaling is monster health - you will have a real balance problem somewhere, though where it is hard to say. In Mass Effect 3 it seems to me that things balance out pretty nicely on Normal difficulty but thugs using guns seem really weak on higher difficulty levels and Biotic Explosions seem super powerful.
Diablo 3 managed to avoid this issue just by virtue of making the sole health-based attack be utterly junk. Monks can blow up enemies for 30% of their health in a small radius but the cost of doing so is high and the difficulty of applying it is substantial so that ability is wretched on low difficulty levels and mediocre in Inferno difficulty. If Blizzard had made the ability usable on Normal it would have been heinously overpowered in Inferno so they managed to do things right in this case - though it seems almost certainly by luck. Blizzard did a really good job avoiding scaling messes in D3 by having absolutely everything scale off of weapon damage and this is the sole problematic exception so I am certainly willing to forgive it!
It shouldn't be said that these scaling issues necessarily wreck games. They are generally fun and make you think about how you want to build your character, which is great, but they do cause havoc when you want to create a really balanced strategy game. In D2 the Necromancer was so overpowered that crazy scaling wrecked the game and needed to be reigned in, even in a game where terrible balance was the norm. I guess it depends what your goal is. If you want really razor edge balance then scaling damage to enemy health is a total mess. If you just want interesting stuff to do and crazy combos for people to figure out it works out fine.