For things like the end-bosses or higher tier stuff, you can't get loot from the Great Vault if you've never killed that boss. Now, that's not a week-by-week thing, there's no I'm going to skip these bosses this week to game the system but you can't just go in with 3 Mythic boss kills under your belt and then get a Denathrius item or Stone generals item. That's not possible. You'll have to have killed him on Mythic at least once before those because valid options. Same for Heroic, same for Normal.