That's a tough one. MDMA, LSD, cannabis and 2C-E are all in contention.
MDMA's a pretty obvious choice. In terms of life-altering decisions that drugs played a direct role in guiding me to, MDMA probably wins.
I only experimented with 2C-E for a couple months, but on two separate 2C-E trips (one of which also included some MDMA), I quit smoking tobacco and decided to go back to school.
LSD has been the most valuable tool for more esoteric knowledge: re-evaluating my life philosophy, coming to terms with my sense of self, etc. I also recently had my first candyflip, and while it's too early to comment on how significant it will prove to be long-term, it was certainly one of the most incredible experiences of my life.
Pot's a tricky one. I use it so frequently that it's hard to attribute specific decisions or outcomes to it. I discovered the joys of THC along with my first serious girlfriend in HS, and in college it helped me come out of my shell and socialize with more people (most people I know from college, I met by sharing a bowl). Since I use it daily and it's such a huge part of my social life, it would certainly be the hardest to give up entirely.