Don't let the storage on your Mac get greater then 90% of the total, leaving at least 10% free. Many operations use the Mac's empty storage space to move files around. If you run out of storage, then those operations may not be able to be completed and, ironically, that can mean that even deleting doesn't work. If you have less than 10% available, then things can get lost forever. This is also true if your iCloud storage space gets low.
I actually found that on my 1 TB MacAir crazy things began to happen when I had only 120GB free. When I transferred enough stuff to external drives, getting to 150 GB free, things cleared up. So now, I limit my storage to only 85% of the total.
External drives are essential not just for backups, but also to move stuff so your internal drive can be worry free.
Oh-- and whatever you do, don't use "Cleaner apps" to automatically dump files on your Mac. They can't be trusted.