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Aviation guarantees mobility, but its emissions also contribute considerably to climate change. Therefore, climate impact mitigation strategies have to be developed based on comprehensive assessments of the different impacting factors. We quantify the climate impact mitigation potential and related costs resulting from changes in aircraft operations and design using a multi-disciplinary model workflow. We first analyze the climate impact mitigation potential and cash operating cost changes of altered cruise altitudes and speeds for all flights globally operated by the Airbus A330-200 fleet in the year 2006. We find that this globally can lead to a 42% reduction in temperature response at a 10% cash operating cost increase. Based on this analysis, new design criteria are derived for future aircraft that are optimized for cruise conditions with reduced climate impact. The newly-optimized aircraft is re-assessed with the developed model workflow. We obtain additional climate mitigation potential with small to moderate cash operating cost changes due to the aircraft design changes of, e.g., a 32% and 54% temperature response reduction for a 0% and 10% cash operating cost increase. Hence, replacing the entire A330-200 fleet by this redesigned aircraft (Ma cr = 0.72 and initial cruise altitude (ICA) = 8000 m) could reduce the climate impact by 32% without an increase of cash operating cost.