Tips for working around those targets with extreme defense:
1) A certain cursed class (won't spoil which) has an ability that removes all defensive buffs on a target. Becomes problematic with speed timing since the target will continuously re-apply buffs at start of turn for free though.....
2) Damage Over Time effects aren't effected by defense buffs. (Burn, Bleed, Lust) Cleric's wide target Fire dmg/debuff is low damage, but hits all and builds up over repeated turns ....
Mage has two options for Burn as well, I think.
Noble and Warrior have attacks with Bleed.
That same cursed class above has two options for Lust damage over time. (1 direct skill, other is a specific weapon)
However, bear in mind an enemy dying to DoT effect doesn't seem to count for some (?) "Kill enemy" goals. ( maybe only certain types, haven't figured out yet )
Because of this, at least a mix of any two of Cleric, (cursed class with high speed), or Noble/Warrior (bleed attack) seem almost required in any party.