The main thing to remember is that resistance always works.
Defense on the other hand, not so much.
Mobs will always have a 5%+ chance to hit you based on their level compared to yours along with if they are above minion.
After so many misses the game forces a hit, so you will get hit.
This does not count mobs with autohit attacks.
Then there is defense debuffs, that can lower your defense unless you are Super Reflexes.
I have been one shot in a SSB as a SR tanker with buffed 72% defense.