I'm not sure exactly what you mean by the term "dataset", but I will assume you are asking about co-registering multiple images from different patients (i.e. multiple 3D images per subject).
To answer your questions:
- If there are no obvious choices about which image is best, then a random choice is fine. If you have e.g. a CT and an MRI for each subject, then co-registration using the CT images is likely going to give you better results because of intrinsic image characteristics (e.g. less distortion, image value linked to physical quantity).
- I suppose that depends on what you want to do, but if it is important to have all imaging data in the same co-registered reference space then yes.
Another option is to try and generate an average image, and then use that as a reference to register other images to. Without more information about what you are trying to achieve it's hard to give any more specific advice.