The automotive industry faces development challenges due to emerging technologies, regulatory demands, societal trends, and evolving customer mobility needs. These factors contribute to a wide range of vehicle variants and increasingly complex powertrains. The layout of a vehicle is usually based on standardized driving cycles such as WLTC, gradeability, acceleration test cases, and many more. In real-world driving cycles, however, this can lead to limitations under certain boundary conditions. To ensure that all customer requirements are met, vehicle testing is conducted under extreme environmental conditions, e.g., in Sweden or Spain. One way to reduce the development time while ensuring high product quality and cost-effectiveness is to use model-based methods for the comprehensive design of powertrains. This study presents a layout methodology using a top-down approach. Initially, powertrain-relevant requirements for an exemplary target customer are translated into a specification sheet with specific test cases. An overall vehicle model with detailed thermal sub-models is developed to evaluate the different requirements. A baseline design for a C-segment plug-in hybrid vehicle was developed as part of the FVV research project HyFlex-ICE using standardized test cases, highlighting the influence of customer profiles on the design outcome through varying weighting factors. The target customer’s design is analyzed in four real driving scenarios, considering variations in parameters such as the ambient temperature, traffic, driver type, trailer pulling, and battery state-of-charge, to assess their influence on the target variables. In the next step, the potential of hardware technologies and predictive driving functions is examined in selected driving scenarios based on the identified constraints of the baseline design. As a result, four application-specific technology packages (Cost neutral, Cold country, Hot country, and Premium) for different customer requirements and sales markets are defined, which, finally, demonstrates the applicability of the holistic methodology.