Depends on how the difficulty increases work.
If it's something like "enemies do double damage" then that's not really interesting.
If it's something like, 'there will be some extra enemies and they'll be designed a bit tougher in general" then that feels a bit more interesting.
Less "fake" in a way.
My first play will probably be Path of the Damned, Expert Mode, Trial of Iron, just to see how far I can get.
Then probably tone is down and take off Trial of Iron.
If I have to resort to cheapness, then I'll definitely end up lowering difficulty.
Not too interested in most extra challenges in this sort of game.
Much more interested in "challenging" stuff in a game less focused on requisite stat growth, and something more like a Legend of Zelda or Megaman and your goal is "make it through the game without taking a single hit". A game like, say, Skyrim, you're *going* to take hits no matter what so you better have some hp, unless you want to be really cheap.