Many spinel intercalation compounds are well known for their high ionic conductivity and high voltage in Li-ion batteries. In this study, we investigate the effects of changing the (i) guest cation valence, (ii) guest cation size, and (iii) host ionicity on the site preference and, in turn, intercalation behavior of spinel compounds. We examine the model spinels of CoO₂ and TiS₂ from first-principles and choose intercalants of Li, Na, and Mg to investigate the parameters of interest. Our results indicate that larger guest cations prefer octahedral coordination of anions within the spinel framework. Electrostatic interactions cause the guest cations to reside on tetrahedral sites within the spinel framework for spinel hosts that are more ionic in nature. These competing factors dictate the site preference and electrochemical properties of spinel intercalation compounds. We propose simple design principles that suggest that Na intercalation into Co, Ni, or Mn oxide spinels would result in fast sodium ion diffusion and therefore make them promising candidates for Na-ion batteries.