I doesn't use any macros nor different profiles for my shaman. In my primary spec is everything works as intended, I don't have to change target to cast any damaging or healing or utility spells, just mouse-over and cast. However, if I switch to secondary spec, some spells won't work, waiting me to target my intended target for some spells, while others work flawlessly still.
Weirdest about this, if I exit the game completely while still on secondary spec, log back in, everything works fine UNTIL either a reload happens, like entering an instance or just simply moving the trouble spells around the cast bars.
Switching back to primary spec, mouse-over casting still working as intended. I didn't found differences in any meaningful options between specs.

It took me 4 days to realise, I was dumb, and the source of the problem was that I didn't replaced the spell buttons on my castbars with the highest rank versions. Replacing them solves the mouse-over casting issue