The most cited chronic fault is the plastic coolant fittings, which become brittle in the hot engine bay; one owner replaced them with brass so they would last the life of the car. Turbo coolant lines are flagged as a common replacement around higher mileage, and coolant-system work is a recurring expense.
Brittle plastic coolant fittings and coolant system
Mercedes-Benz E63 AMG (W212) · mechanical