The difficulty ladder in Guildrun
Above the base game Guildrun stacks six difficulty levels, C through SSS, and each one adds a rule rather than just more enemy health. Heroes start combats damaged, enemies get tougher, Shards per survivor drop, and at S a hero can only equip one item per rank.
At SSS the act bosses reach into the fights before them, attaching a relic of their own to specific stages, which is listed in full on this page.