The paper describes a new methodology for simulation and evaluating human-machine interaction in aircraft cockpits with the objective to assess the impact of a new system design on overall flight crew performance. The methodology shall allow to assess multiple performance criteria and to derive needed design improvements more accurately and earlier (in the development process) and with reduced effort compared to existing approaches. The main technical enabler is a cognitive model of pilot behaviour. The focus of the paper is on the application of the new methodology for simulating and evaluating the interaction with a 4D Advanced Flight Management System.