My main character is a complete tank, taking warfare as his primary mastery and defense as his secondary. Adrenaline boosts his healing rate more frequently than you might think (5% chance, but it sure goes off a lot). Quick Recovery helps him wade into large groups of foes and not lose his shield protection. Focus ups his chance of shield block, which means less damage and more survivability. There are just so many ways the defense mastery is a great second; they're practically made for each other.
The only negative comment I can make is that I focused too much on melee combat. The end boss from the original game gave my main character fits because he does so much damage in melee range. I basically had to run around plinking with a bow and dodging attacks, running in close for a big hit every now and then, while sucking down potions. It made that boss battle a lot more stressful. Other than that, though, my tank waded through the game slaughtering pretty much everything else with gleeful abandon. You should take a look at the following site, which gives you stats on all the masteries: