I am not sure really what you are trying to accomplish here, but for the purpose of drawing ROIs, you can draw on a finer resolution grid and then use 3dresample or 3dfractionize to put the data into another grid. Also each of these programs offer multiple options for interpolation - linear, cubic, quintic, heptic, fourier, nearest neighbor. See the help for each program to get more information.
The AFNI GUI also offers options for on-the-fly interpolation for the overlay and threshold data in the Define Datamode menu. Using the Zoom feature in AFNI image windows uses linear interpolation by default, but this can be controlled by the AFNI environment variable AFNI_IMAGE_ZOOM_NN to change it to nearest neighbor, but that would make zooming "blockier" but reflect the actual voxels better.
