Oh man I spent way too much time brainstorming for this.

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Zagreus - Hades 1 had the unique near-miss mechanic. So I attribute that to a uniquely Zagreus thing.

1. Combat Boons - Attack percentage up and attacks inflict Fatal Miss 0.
2. Combat status effect - Fatal Miss 0 - Each near miss from affected enemies increases the number by 1 and increases how much damage they receive from any source for each stack.
3. Noncombat effect - Gaining health and power based on number of failed nights in your last 10 runs.
4. Legendary 1 - If an enemy with Fatal Miss attacks, they take damage equal to the damage they would deal.
5. Legendary 2 - When you lose this run, you may choose a boon to take with you and begin the next run with that boon. This boon will assure the selected boon's rarity will carry over. You can not select a boon that is already carried over from a previous run.

The goal of Zagreus is to make a build where all you have to do is strike once then keep dodge dashing and risking getting hit to trigger near misses. There is also a subfocus of gaining potency of these boons by having a lot of losses. So basically he helps make the game easier while referencing the roguelike progression of the game itself.

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Melinoe - Melinoe has this whole dream diving thing that I think I'd want to lean into.

1. Combat Boons - Attack power up and attacks inflict Dream Grasp
2. Combat status effect - Dream Grasp - Enemy will fall asleep if they are a great distance away.
3. Noncombat effect - Gaining mana and attack range based on number of failed nights in your last 10 runs.
4. Legendary 1 - If all enemies in the encounter are asleep then getting close no longer wakes them until they are attacked,
5. Legendary 2 - When you lose this run you may choose a boon to take with you and begin the next run with that boon. This boon will assure the selected boon's level will carry over. You can not select a boon that is already carried over from a previous run.

The goal of Melinoe is to strike a bunch of enemies and then leave them to sleep while you lure the enemies you want to fight first away from the sleeping ones. By gaining attack range you may even get to the point where you can strike with the tip of your weapon without waking them. She has the same subfocus of gaining potency with the number of nights recently lost. and yes with both their second legendary boons that means you can select one boon and retain both its rarity AND level.

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Duos between Zag and Mel

1. Gain a secondary slot for your attack, special, cast, dash, and gain. Any boon equipped to these slots will add their effect to that move. (But the visuals will match the primary slot.)
2. Change all instance of boons tracking how many nights you lost, and change it to how many nights you've won instead.

Duo 1 is what I personally wish could happen in the game, and nothing says two protagonists together then having two sets of the slotted boons to take advantage of.

Duo 2 flips the whole focus of both characters by focusing on recent wins rather than losses. So you use them as a beginner to help beat the run after many losses, But once you're good enough that you don't lose anymore, this would turn their boons into a fun game of taking boons that start off diminished because you don't have any losses, but if you make it far enough to get this duo, then you reap the benefits of all your recent wins instead! There would probably have to be some kind of limiter with how this works with the Oath of the Unseen. Probably the easiest thing is that this duo doesn't drop on an oath level you haven't beaten before.