Human error is one of the primary reasons for accidents in complex industries like aviation, nuclear power plant management, and health care. Physical and cognitive workload, flawed information processing, and poor decision making are some of the reasons that make humans vulnerable to error and lead to failures and accidents. In many accidents and failures, oftentimes, vulnerabilities that are embedded in the system, in the form of design deficiencies and poor human factors, lead to latent or catastrophic failures, but the last link is a human operator who gets blamed or worse, injured. This paper introduces an early design human performance assessment framework to identify what type of digital prototyping methodologies are appropriate to detect the deviation of the operator's performance due to an emergency condition. Fire in a civilian aircraft cockpit was introduced as a performance shaping factor (PSF). Ergonomics performance was evaluated using two prototyping strategies: (1) a computational prototyping framework includes digital human modeling (DHM) and computer-aided design; and (2) a novel mixed prototyping framework includes motion capture, DHM, and virtual reality. Results showed that the mixed prototyping framework can simulate emergency scenarios with increased realism and also has the potential to incorporate subjective aspects of ergonomics outcomes, overcoming the underlying lack of design knowledge in conventional early design methodologies.