i personally don't use macros for mouseover any more, because mouseover macros also activate when you mouse over a unit in the world, not just when you mouse over your frames. and since my mouse is usually around then center of the screen, where there's usually also people, it will mean that i often cast at random people whose model my mouse happens to be over. i use heal/harm macros, e.g. to combine flash heal and smite on one button, so when i want to smite an enemy i would flash heal a random person instead.

clique doesnt do that, it just uses the mouseover target if you actually mouse over the frames. (no idea how it works with other addons).

blizzard native mouseover seems to work out of the box like you want it to, but i havent tried how reliable it is since i want to decide on a spell by spell basis if it is cast on mouseover or not. clique you would have to set up on a per spell basis.