Previously, we studied whether vanadium-based intermediates are faithful mimics of native non-heme iron halogenases and found differences between non-heme iron halogenase active site structures and those of their vanadium-based mimics. In this study, we compare native ferryl species and their vanadyl mimics for the related non-heme iron hydroxylases. We highlight the limits of using vanadyl mimics for the fleeting ferryl intermediates in C-H hydroxylation through an extensive computational study of isomer structures and energetics in hydroxylases and find even starker differences between Fe and V active site models than for halogenases. While the isomerization energy landscape of V(IV)=O is barrierless in our models, we observe a barrier for isomerization of Fe(IV)=O in hydroxylases that is higher than that observed in non-heme iron halogenases. Additionally, the hydroxylase active site isomerization barrier for structures with monodentate Glu is lower relative to bidentate Glu isomers. This suggests that targeted modifications to the enzyme active site to favor monodentate Glu, e.g., through noncovalent interactions, could preferentially lower the isomerization barrier in engineered hydroxylases.