This paper presents a systematic study that illustrates the importance of the topologies of microchannels on electrokinetically based separation. Using theoretical and numerical analyses, we designed and showed that topologies that significantly increased the surface-to-volume ratio of the channel can provide dramatic improvement in the ability of the channel both to dissipate the heat generated by Joule heating and to reduce the axial dispersion associated with the siphoning effect. The incremental benefit and tradeoff of geometric complexity was also evaluated. The improvement offered by topographically patterned channels, such as finned structures, is especially pertinent in the development of preparative or semi-preparative scale electrokinetically driven separations, such as capillary electrophoresis and capillary electrochromatography, in which large cross sections of channels are required to achieve the needed volumetric throughput.