Oh, great question. I'd have to say that there are two huge changes in Pi's life. One is of course the accident that isolates Pi on the raft. That changed literally every aspect of his life, from who he was with to how he saw the world, even what and when he ate and slept.
But if you want a single greatest change, I'd say it is when he encounters the stranger on the raft and then kills him. In Chapter 90 Pi thinks to himself "Something in me died then that has never come back to life." He had managed to keep that nameless thing alive throughout the entire ordeal until that time, but killing a human (and using his flesh for bait/perhaps eating him directly) changed him.