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Not sure what you mean by 'better loot'. The only thing that increased difficulty does is increase drop rates of materials and increased experience earned.
That's it. Equipable items (loot) has a 100% drop chance and is always the same.
As for the OP: Do whatever you're comfortable with. For the most part, the added difficulty is only there for the challenge. Aside form a few specific examples: for instance there's a gun that can only be obtained on hardcore mode AND on verteran difficulty or higher. Another example is a sword that can only be obtained by completing a campaign run on apocalypse.
True but it also depends of your total archetype level (76 for Mythic tier).