With multiple selection, you have to wait before clicking on key object
Illustrator CC 2018
With a multiple selection, if the last object you click is the one you want to align to, you have to wait a little bit before re-clicking to set it as key object, otherwise it will go into Isolation mode or Symbol edition mode (if it's a Symbol).
You can tweak the double click speed in Windows settings or disable 'Double Click To Isolate' option in Illustrator’s Preferences > General.
Welcome back :)
Stéphanie Noverraz commented
Could have been that, I can't say because I'm back on a Mac now and it's working fine. :)
Stéphanie, it’s because the Windows settings for the speed of double click. If you make the allowed pause shorter, Ai will stop misfiring Isolation mode — but it’d be harder for you to double-click elsewhere.
I personally suffered from this for a while, before I realized I can tweak it, since I'm fast enough to do quick double-clicks... and also I learnt to wait a bit before setting a key :)
As a workaround you can disable 'Double Click To Isolate' option in Preferences > General.