The only problem I've ever had was having to re enter passwords being on web pages. In the past when I was using Google's browser Sync.
I went back to Foxmarks and it's not a problem anymore.
I use Cleanup!, ATF-Cleaner and Ccleaner.
Not necessarily in that order.
Plus GlaryUtilities, RegSeeker and AdvancedPersonalCarev2 at times.
Cleanup! is the deepest cleaner, prompting to log off to complete the clean. Which also makes it the most volatile if you don't know what you are cleaning out.
Most of the time I just use ATF-Cleaner and that's enough.
I run Ccleaner's registry scan to see how it's doing.
If it finds a lot I'll use RegSeeker which cleans deeper.
Anyway, for me and my computers it takes a load off the cpu by 5-40% at variable times. 40% - 80% spikes mainly. After cleaning I idle at arounnd 5% as opposed to 5-40% and more before cleaning.
The difference is noticeable on these two p3's, though I doubt if a core duo or quad would notice.
I have had nothing bad happen with all these tools in using either one or all of them.
One Cleaner will not get it all. I know because I can run one then another and pick up more. Files and registry entries.
Make a backup of your registry before cleaning it, to be sure you won't mess something up. I don't anymore, being confident in the tools. But with some other programs that I don't have and others do, I'd backup the registry.
As opposed to most techs advice they would say don't clean the registry. I do and see a difference in performance. So it depends on the person, computer and programs I suppose.
fodder's advice is sound for sure. Especially with installing programs, which is why I always 'download' instead of 'run' which operates out of the temp files. Downloading the program, by way of 'Run' downloads to the temp files and installing from there could make your temp files more important then they should be.
That's my opinion and experience.
People with thousands invested in programs would be wise to have 1 or more full backups of the entire system.
Worth the price of a duplicate Hard Drive of the same size imo.