Mac OS automatically defrags files up to 20 MB on the fly; unless you regularly process/edit large file sizes such as videos or pics in RAW format, there is rarely a need to do so.
Additionally, most applications are installed in one neat package - you throw that out, you've deleted 99% of it; the only exception are the very small preferences files in your Library or if you installed something like Adobe which I've heard places files everywhere. In that case, it's best to use their uninstaller to get rid of all of it.
As for cleaning, Onyx works but there is no need to run it very often. Another excellent application to work on the directories is Disk Warrior (by Alsoft, latest version is 4.4) - I run that occasionally. Absolutely stay away from things like MacKeeper (should be labeled malware) or other so-called "cleaning" utilities. A lot of them do more harm than good and most are completely superfluous. Onyx is free; DW does cost money.
If there is one available, using an applications uninstaller is best, although often there isn't one provided.
If that's the case, here's a useful free app that deletes applications/widgets/plugins and their associated files:
It may leave some bits behind, but it does a pretty good job.
Get EasyFind (looks like it's only available directly from the App Store now. That's a shame.)
EDIT You can get from MacUpdate
(Spotlight/Finder won't work well for this.) Set it to scan all files, files and folders, case insensitive, invisible. Enter the name of the app, the developer or any other way it might be identified. Search using phrase, all words, and boolean.
You can use Destroy from the EasyFind Menu. But if it's a file that requires a password (you'll know it is if nothing happens when you "Destroy"), then select the file/folder use Reveal in Finder, select the file>move to trash>and enter your password at the prompt.
Be careful not to delete anything that is part of a Shared Lilbrary; i.e. used by some other applicaton.
For very complicated applications with files all over the system, best to rely on the provided uninstaller, if possible.
For very simple applications, just move the app to the Trash. Searching with EasyFind, you will probably find a few other, small items in your /User/Library. These can be deleted with no harmful consequences.
Message was edited by: WZZZ