Poison. Just one word could change everything. I thought up a clause while working and thinking about Nuzlocke at the same time. So this here may change or preserve the difficulty. Keep in mind though, this clause's effects are different depending on what Gen version of the game it's applied.

• Generation I, II, and III: The pokemon that fainted to poison does not count as a death. This rule here won't be used as much since its a safety net rule.

• Generation IV: If your pokemon is left with 1 HP and the poison fades away, its dead. Do whatever you do with dead pokemon. I could see this rule being applied to up the difficulty (after all, Nuzlocke is MEANT to be hard).

• Generation V and onward: Nothing. You don't need a rule for this since its effect was removed in-field.

Poison in a nutshell.