a couple of things that i think would cut out the need for a mega mule dupe/hack in DS2, or at least make it less of a thing anyway.
…a way to de-level your character, you wouldn't get back spent souls. think soul suck from Demon's Souls.
…you only need one copy of any spell and can attune it as many times as you have attunement slots available or you have MP that governs castings instead of x number of casting per attunement.
…you can purchase all farmable items (only farmable items, not one of or unique items) from an unlockable/secret merchant. some things would still have to be of a limited number.
…a test/debug room (like in TES Oblivion) that you could access/unlock that had all weapons and armor in it, already fully upgraded. you can only access it while in some sort of gladiator style challenge arena type thingy and you wouldn't be able to take the items with you when you left the arena. this could be extremely viable for PVE and build testing and you could give rewards (blessings, spells, slabs, uniques, whatever) for beating gladiator style challenges.
there, that would pretty much address everyones problem with the PVE grind and the desire for some sort of mega dupe glitch.