Casting this hex on multiple foes that are within the same area of effect will compound the amount of damage caused to all the foes in the group. Arcane Echo can be used to help facilitate this tactic.
Damage from this hex is applied before the skill actually activates or the attack actually hits. For example, a self-heal will trigger Spiteful Spirit before the heal occurs.
Because of the way Hero AI picks targets, they will usually not use it as often as needed for maximum effect.
This skill is very powerful in hard mode as it benefits from the attack and casting speed bonuses foes have.
For some multiple-hit attacks such as Cyclone Axe or Whirlwind Attack, Spiteful Spirit will only trigger once, rather than once for each attack made. However, Barrage and Volley trigger once on skill use as well as one additional time for each arrow fired.