If by safe updater you mean this:
http://gbatemp.net/index.php?showtopic=184057
And by xzxero's guide, you mean this:
http://gbatemp.net/index.php?showtopic=171901
Then xzxero's is just a manual install/update. Like already mentioned, you won't loose Bootmii, cIOSes or softmods (preloader/CIOSCORP).
However, if you use the safe updater, you will be doing an official update through Nintendo but you won't loose Bootmii or cIOSes. In both cases boot2 will be left alone but you will loose any softmods.
So, guide = more involved but saves preloader/CIOSCORP.
SU = easier but looses preloader/CIOSCORP.
Depends on what you need/want.