In the present paper, we consider the employment of working-fluid mixtures in organic Rankine cycle (ORC) systems with respect to thermodynamic and heat-transfer performance, component sizing and capital costs. The selected working-fluid mixtures promise reduced exergy losses due to their non-isothermal phase-change behaviour, and thus improved cycle efficiencies and power outputs over their respective pure-fluid components. A multi-objective cost-power optimization of a specific low-temperature ORC system (operating with geothermal water at 98 °C) reveals that the use of working-fluid-mixtures does indeed show a thermodynamic improvement over the pure-fluids. At the same time, heat transfer and cost analyses, however, suggest that it also requires larger evaporators, condensers and expanders; thus, the resulting ORC systems are also associated with higher costs. In particular, 50% n-pentane + 50% n-hexane and 60% R-245fa + 40% R-227ea mixtures lead to the thermodynamically optimal cycles, whereas pure n-pentane and pure R-245fa have lower plant costs, both estimated as having ∼14% lower costs per unit power output compared to the thermodynamically optimal mixtures. These conclusions highlight the importance of using system cost minimization as a design objective for ORC plants.