Man, it's been a while since I touched this idea, and now I've got a wild idea to just bundle all my 'fantasy RPG heartbreaker' ideas into one book: a megadungeon with showcase dungeon adventures, using 5e rules but with a suite of custom classes designed specifically for the campaign.
Wild classes.
Like, screw 'fighter.' No, you're a 'fusilier' with mastery of mount and musket. Forget 'cleric.' You're a 'penitent,' deriving divine power from a great sin you are seek to redeem yourself for. No time for a 'wizard.' You're a 'rhabdomancer,' crafting wands from magic items you destroy and from the remains of creatures you kill. There are no 'rogues' here: you are a 'leper,' diseased and deadly.
Or I could be goofy, and make classes like 'mushroom man' and 'roofer.' What does a 20th level 'roofer' look like? I dunno. He probably throws very lethal shingles.
Like, design monsters specifically to do cool things in relationship to PC abilities, and design PC abilities to combo, and to unlock certain tricks as you level up to make the Metroidvania gating possible. Rather than being a supplement to an existing game -- like a new episode of the TV series we watch each week -- make it more like a special event mini-series prestige HBO thing.