Many times when someone plays Blitzcrank they usually preform the following combo:
Q (Rocket Grab) --> E (Power Fist) --> E (Again After CDs) --> W (OverDrive to catch the enemy) and then finally they use his R (Ultimate).
 
While that is a good way to take down opponents the best way to utilize his ultimate is not for the damage but for the silence. For example,
You are in Bottom lane and you're lanning against Taric or Sion (someone with a stun or heal). A good Taric would wait till you get him down to around 75% HP before healing. When you see him go below 80%ish that's when you use your ultimate!
 
Too Long Did Not Read (Tl;DR):
Know your enemy, and predict when he is about to heal/stun you and blow your ultimate and your full combo. Which is if you forgot:
Close Range: W -> E-> E-> (If their far away Q them back in) -> R
Long Range: Q -> E -> W -> E -> R