Eight Ru-containing single crystal Ni-base superalloys were devised and evaluated using a design of experiments approach to isolate the effects of four elements, namely Co, Mo, W and Ru, on creep, plain low-cycle fatigue (LCF), 1100°C cyclic oxidation and thermal barrier coating (TBC) compatibility. All the alloys compared favourably to CMSX-4 mechanically, however, they underperformed in oxidation. Mo and Co were found to adversely affect both the cyclic oxidation performance and TBC compatibility. None of the four factorials were found to have a statistically significant impact on LCF. In general, the largest creep temperature benefits over CMSX-4 were observed at low (<800˚C) and high (>1000˚C) temperatures. At intermediate temperatures (~ 850˚C to 950˚C) the improvement in temperature capability was less pronounced. Mo was found to have the only statistically significant contribution on creep. Consistent with the correlation between lattice misfit and creep, the impact was positive at low temperatures/high stresses and negative at intermediate conditions. As misfit increases in low temperature creep the density of dislocations in the γ′ decreases and the number of stacking faults in the γ channels increases. The latter culminates in a negative misfit threshold above which primary creep is effectively 'turned off'. Under intermediate creep conditions, high negative misfit alloys spontaneously develop a 'labyrinth' structure that comprises approximately equal numbers of rafts in all three <001> directions irrespective of the direction of the applied stress. This tendency for labyrinth rafting imposes an upper limit on the magnitude of the negative misfit and thus the degree to which the γ-matrix can be usefully strengthened with refractory elements at intermediate temperatures.