The Core One uses a "CoreXY" system where the extruder moves in X and Y directions instead of X and Z, and the bed moves in Z instead of Y. It eliminates issues

The Core One uses a "CoreXY" system where the extruder moves in X and Y directions instead of X and Z, and the bed moves in Z instead of Y. It eliminates issues caused by large prints progressively increasing the mass/momentum on the Y axis, but it requires a more complex system of belts. Also, the Core One only comes in an enclosure, which is good for some materials that need warmer air, but can hinder PLA, which needs cool air. Generally, it seems like if you just want to reliably print PLA, get a MK4S, but if you want the temp-controlled enclosure or filament versatility, get a Core One.