I think I know the problem you are referring to. First, I will tell you how I deal with it. Your multiple image issue adds a complexity, but I will tell you also how I think you can deal with that.

I have found that different programs do actually handle all of these images differently, and the only way I have found to work with them consistently is to insist all of my steps work with Analyze images in an axial orientation. Nifty just doesn't work the same in every program even though "it should".
-First, to be clear, most of my images when I convert Dicoms to Analyze with MRIconvert or with ImageJ, are flipped on the y axis in BIS. I usually do not alter this for things like coregistrations, thresholds, etc in BIS because it doesn't matter. However for ISAS it is necessary to flip the images on the y axis to get them in the same orientation as the MNI template in order to do the analysis. So be sure your orientations match the MNI template before you start. But you will need to reorient the resulting diff images/blobs when you finish in order to see them correctly in other programs including SPM. That is tricky because the diff blob ISAS creates is actually not in the same orientation as other images even though it looks correct in BIS.
-The ISAS analysis puts the diff blob in the MNI space.  You may want to leave it at this, but more on that later. I want it in the patient space, so I put the blob in one of the viewers, bring up the Transformations dialog, select the "Inverse" transformation that ISAS made, apply the Inverse transformation to the blobs, copy Result to Image, and save as "patientBlob" or something meaningful. The blob is now an Analyze image in the patient space for the BIS/ISAS purpose.
-Now I need to be sure this new blob matches the original orientation of my starting images. It doesn't. Something BIS does creates these flipped wrongly in other programs, and simply flipping on y doesn't bring them into the orientation I would expect. I haven't fussed with this too much in BIS. The simplest way to match the orientations is to bring both my reference T1 and patientBlob into Amide where you can see how both are oriented easily, and "rotate" (right click) the patientBlob only with "invert axis" on both x and z axis. This gets the image back to the orientation I started with (and which was inverted on y in BIS). Show only the blob in Amide, Export Data Set (all visible slices, analyze format (SPM)) and this newly reoriented image then saves in the orientation I began with (before I flipped my original Analyze image converted from dicoms into BIS MNI orientation) and works fine in other programs.

You have 2 other issues:
-The images for your patient group all need to be coregistered with one another. I would not recommend choosing one of the patient images for this. Why not leave them all coregistered to MNI template? They need to be coregistered to that anyway in SPM. This is the same template image used by SPM analysis. Then this could skip bringing the images back to the patient space as I described in the last step above. You should still check that the group's blobs match the MNI template orientation in an external program like Amide. If not, fix this first. Now the MNI template and all of your blobs should be in the same orientation.
-Verify this in SPM as well. If it is not true you can always specify a different reference image for your SPM analysis. But orientation has to match as a prerequisite.
-Finally, you need to be sure the images you use in SPM have a center specified, typically at the posterior commissure. BIS does not create this or use it, but it is necessary in SPM. You can do much of the reorientation and set the center from within the SPM tools, but I won't go into that since it depends on the analysis you have set up there. If center and orientation match the MNI template used in SPM everything works fine. So, to answer your question (Should I perform an extra step to get the position/rotation right?), yes, you have to, but it depends on which images you begin with. their file format, and how you save them.