I Nuzlocked this earlier, was a cinch and I sorta felt hollow about it. Next time I do it I'll disable the EXP Share for sure (the extra grinding leads to more "OMGosh!" moments where crits and such can disable a pokemon).
You might try a Wonder Trade Nuzlocke, where you immediately Wonder Trade your 'mon out when you catch 'em, that could be fun.
Another good rule for this gen is "No running away." since it makes the Swarm fights more tense. Your mileage may vary though.