Completely removing apps with CleanMyMac or AppCleaner is useful. Like cleaning browser history with CCleaner (on the other hand, why not just use separate accounts and fast account switching). Or all the stuff that OnyX does, these are troubleshooting steps at best and not needed for babysitting your Mac, or potentially harmful (but the guy removed most things you can use to trash your macOS installation). I guess if you temporarily need some more storage it's nice to have. I think most of that stuff is useless, like cleaning caches and logs, they'll be rebuilt and that makes restarting an app or OS slower. plist files and application folders are easily accessible and neatly separated, I have no trouble at all. If it looks like bloat n' fluff (google helpers for example) I throw 'em off my system. If it looks like programs might use it (Python for example, or Applescript) I don't touch it.

I am sure there are some things on my Mac I might potentially remove without doing harm, but I err on the side of caution as some packages are installed through dependencies. Just don't let it pile up till you can't even be arsed to think about cleaning anymore -) If you check in once or twice a year it's more than enough. Not due to malware infestation, but mostly due to removing applications (and still finding their settings in /Library or ~/Library), Safari extensions I used to run but are no longer up-to-date, helpers running in the background I no longer need or OS updates breaking compatibility. I don't use cleaner, but I do perform the occasional maintenance.

Onyx for mac 10.12.6