head to head
Neither is simply harder - they are hard in different places. Hades demands more execution; The Binding of Isaac: Rebirth demands more variance.

Optimization · Practiced Mastery
An action roguelike about building boon synergies while dodging scripted encounters.

Variance · Systems & Chaos
A twin-stick roguelike won by recognizing which item combinations break the game.
Hades leans Optimization (Practiced Mastery); The Binding of Isaac: Rebirth leans Variance (Systems & Chaos).
Hades leans clearly harder on execution.
Hades
Dash-attack timing and dodging drive moment-to-moment fights.
The Binding of Isaac: Rebirth
Twin-stick aim and dodging matter but pace is forgiving.
Hades leans a little harder on reads, though the gap is small.
Hades
Enemies and bosses use scripted patterns, not adaptation.
The Binding of Isaac: Rebirth
Enemies and bosses scripted; no adaptive opponent.
The Binding of Isaac: Rebirth leans clearly harder on variance.
Hades
Boon offers and room rewards randomise each run.
The Binding of Isaac: Rebirth
Item pools and room generation drive run identity.
Hades leans a little harder on optimization, though the gap is small.
Hades
Build synergies and weapon aspects are deep solvable theory.
The Binding of Isaac: Rebirth
Item synergy knowledge defines whether runs snowball.
A matching score does not mean a matching test. Two games can both sit at 10 on execution and demand completely different things of you - which is why the reasoning above matters more than the number beside it.