If space and WAF dictate bookshelf speakers, go with the BS22 and C22 for LCR and BS21 for S and RS.
The difference between the BS21/41/C21 and BS22/FS52/C22 is that in the second gen improves on the first gen drivers. Further, there is tweaking to improve mid bass quality and the speaker is flatter in mid range. Folks that have listened to both generations of speakers have proclaimed that the second gen is a justifiable step up. You can peruse
this discussion on Pio AJ speakers at your leisure.
The BS41/CC21 will play louder than BS22/CC22, but the 22 have the potential to sound better once set up properly.