Ping.

I have a hard time with it, I usually play with 80-100 ping and I've gotten used to it, but my ping is by no measure 'good'. Sometimes I lag to 200+, I have a hard time playing the game well, but I suppose it's possible to get used to it to some degree, but you will be at a pretty significant disadvantage.

I play on 120 and I always feel lacking in something, some things with some champs players who have lower ping just do better.