Yes dasudevil, it sounds like alot of stuff to do just to defrag but, I think it is best to get rid of all the junk files by running spyscans, antivirus scans and disk clean ups. This way you won't be wasting time and disk space by organizing junk files. It can really add time to a defrag depending on how many of these files you have on your computer. Also, I turn the system restore off because if you don't, all those junk files will still be in the restore file including any spyware and viruses you may have. By defraging in safe mode with only the bare minimum of programs running you get a maximum amount of files optimized. If you just go to the start menu, accessories, system tools, defrag... you still have many programs running in the background and whatever programs and processes are running cannot be defragmented.
Even if you skipped turning off the Pagefile and startups and processes, by defraging in safe mode and shutting off the restore will still give you a better defrag.
I'm trying to remember where I learned this way of doing it. I believe it was from www.langalist.com newsletter. I'll look for the link and post it for you.
And to answer your question... they are both safe for your system. One is just more thourogh than the other. Besides, you have to do spy scans virus scans and dump junk temp files anyway so I do it all at one time about every other week or every week, depending on how much I have used my computer. Hope this is of some help.