Revamp Gehennom by making its main branch substantially shorter, a “hub” branch containing stairs or portals to a bunch of sub-branches containing demon lords’ lairs. Most of the lairs are optional, but at least some of them are required in order to enter the Sanctum. Each demon lord that you don’t kill, however, incurs a unique, harsh effect or debuff on you once you have the Amulet. Suggested ones include:

• The mysterious force, as it exists in vanilla.
• When you try to ascend the stairs, they vanish and several illusory copies of stairs appear across the level, along with one real one which you have to find.
• Walls extrude from existing walls around the hero in random directions, never entirely closing off, via a cellular automaton that looks for walls with a 3x2 area of walkable spaces in front of them, with the space directly in front a regular floor space - the effect of this given enough iterations turns the terrain around you into a maze.
• Generic damage over time, not severe but enough to provide a headwind. Or partial or total disabling of natural regeneration.
• Asmodeus: Some damaging cold effect that happens periodically, or your cold resistance is nullified and replaced with a vulnerability to cold effects.
• Baalzebub: Something to do with insects, either periodic summon insects from nowhere or stronger/more frequent insects
• Juiblex: You may randomly become ill, or have your regeneration dampened or something
• Geryon: Hordes of buffed q generate and rampage periodically.

In variants that give Geryon a lair, implement his two-headed dog Orthus.