Hmmm, let's see. My current career game is 220+ mods, all installed by CKAN. No problems.
I don't believe in doing upgrades when a new KSP is released because it takes mod authors a while to get their updates out. So I just make a new install and merrily go along. I use the .ckan file to install all the same mods, if some are missing (ie: not available for the current version yet), I just delete it and move on.
If I had to download 220 mods manually, and update them, it would literally take me days to do that. Instead, I made my latest 1.3.0 install in about 1/2 an hour using CKAN.