head to head
Neither is simply harder - they are hard in different places. Cities: Skylines demands more optimization; Two Point Hospital demands more variance.

Optimization · Pure Optimization
A sandbox city builder that is pure traffic and zoning optimization.

Optimization · Pure Optimization
Comic hospital tycoon optimized by room layouts and staffing.
Cities: Skylines leans Optimization (Pure Optimization); Two Point Hospital leans Optimization (Pure Optimization).
Two Point Hospital leans a little harder on execution, though the gap is small.
Cities: Skylines
No reflex demands at all.
Two Point Hospital
no reflex
Same score on reads - which means the number cannot separate them. The difference is in what each one asks of you.
Cities: Skylines
No adaptive opponent exists in the sandbox.
Two Point Hospital
no adversary
Two Point Hospital leans clearly harder on variance.
Cities: Skylines
Minor disaster events if enabled.
Two Point Hospital
patient illness mix
Cities: Skylines leans clearly harder on optimization.
Cities: Skylines
Traffic flow, zoning, and budgets are fully solvable.
Two Point Hospital
room layouts, staffing, training
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.