head to head
Neither is simply harder - they are hard in different places. Ghostbusters: Sanctum of Slime demands more execution; Grand Theft Auto: San Andreas demands more optimization.

Execution · Practiced Mastery
A twin-stick shooter about aiming and matching weapons to scripted ghost waves.

Optimization · Practiced Mastery
A sprawling open-world crime epic with RPG-style character stats across a whole state.
Ghostbusters: Sanctum of Slime leans Execution (Practiced Mastery); Grand Theft Auto: San Andreas leans Optimization (Practiced Mastery).
Ghostbusters: Sanctum of Slime leans clearly harder on execution.
Ghostbusters: Sanctum of Slime
Twin-stick aiming and dodging lead the combat
Grand Theft Auto: San Andreas
Flying school and drive-bys need decent hands
Ghostbusters: Sanctum of Slime leans a little harder on reads, though the gap is small.
Ghostbusters: Sanctum of Slime
Ghost enemies follow scripted patterns, not adapting
Grand Theft Auto: San Andreas
Gang AI is scripted, never adaptive
Ghostbusters: Sanctum of Slime leans a little harder on variance, though the gap is small.
Ghostbusters: Sanctum of Slime
Enemy spawns and color-matching add some chaos
Grand Theft Auto: San Andreas
Territory wars and traffic add light randomness
Grand Theft Auto: San Andreas leans clearly harder on optimization.
Ghostbusters: Sanctum of Slime
Matching weapon colors to enemies rewards planning
Grand Theft Auto: San Andreas
Stats, gym, weapon skill, and routes reward systematic play
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.