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Since the pick off mirror is located at the side of the light path, the OAG will "see" an area off to the side of the object you are imaging. As a result, if you are imaging a planetary nebula at a long focal length for example, there may be no star in that area bright enough to guide on with suitably short exposures. Rotating the OAG/guide camera assembly around until a suitable guide star could be found would be necessary, while you will need to be aware of what (albeit small) impact this may have on your balance and also plan your geometry to prevent mount collisions.
You may also need to retake flats if the pickoff mirror causes partial vignetting of the imaging sensor due to obstruction of the light path, as the position of that vignetting will have changed with the rotation. However, I think the pickoff mirror is usually far enough to the side that this isn't an issue, however if your optics have a particularly large amount of coma they may blur the field enough that an OAG is not suitable.
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