Unlocking progression tiers
To know which named targets are required to kill before unlocking the next progression tier, you can talk to the Tier NPC guides in the Guild Lobby’s eastern room. Any other targets not mentioned are optional.
Upon killing one of the required targets for progression, a “ghost” form of the target will appear. It is very weak, slap it around and loot its keys. Finally, head back to the Guild Lobby and speak to the Keymaster called “Vinz Clortho”, in the center area, on the left. Give him the key you looted and he will unlock new zones for you to progress into, as well as reward you with special charms giving good bonus stats and special clicky abilities for each different key you give him.