Solving strategic IMO tasks for the decarbonization of maritime transport and the dynamics of its controlling indicators (EEDI, EEXI, CII) involves the comprehensive use of renewable and low-carbon fuels (LNG, biodiesel, methanol in the mid-term perspective of 2030, ammonia, and hydrogen to achieve zero emissions by 2050) and energy-saving technologies. The technology of regenerating secondary heat sources of the ship’s power plant WHR in the form of an Organic Rankine Cycle (ORC) is considered one of the most promising solutions. The attractiveness of the ORC is justified by the share of the energy potential of WHR at 45–50%, almost half of which are low-temperature WHR (80–90 °C and below). However, according to DNV GL, the widespread adoption of WHR-ORC technologies, especially on operating ships, is hindered by the statistical lack of system prototypes combined with the high cost of implementation. Developing methodological tools for justifying the energy efficiency indicators of WHR–ORC cycle implementation is relevant at all stages of design. The methodological solutions proposed in this article are focused on the initial stages of comparative evaluation of alternative structural solutions (without the need to use detailed technical data of the ship’s systems, power plant, and ORC nodes), expected indicators of energy efficiency, and cycle performance. The development is based on generalized results of variation studies of the ORC in the structure of the widely used main marine medium-speed diesel engine Wärtsilä 12V46F (14,400 kW, 500 min−1) in the operational load cycle range of 25–100% of nominal power. The algorithm of the proposed solutions is based on the established interrelationship of the components of the ORC energy balance in the P-h diagram field of thermodynamic indicators of the cycle working fluid (R134a was used). The implemented strategy does allow, in graphical form, for justifying the choice of working fluid and evaluating the energy performance and efficiency of alternative WHR sources for the main engine, taking into account the design solutions of the power turbine and the technological constraints of the ORC condensation system. The verification of the developed methodological solutions is served by the results of comprehensive variation studies of the ORC performed by the authors using the professionally oriented thermoengineering tool “Thermoflow” and the specification data of Wärtsilä 12V46F with an achieved increase in energy efficiency indicators by 21.4–7%.