I’m having an issue with keybinding.
Any macro I put on my mousewheel click bind will not work when trying to mouseover someone
At first I thought it was my macros but they work fine for mouseover if I put them on a different button
So what’s going on? I just want my mousewheel click to be a useable keybind 
Unitframes eat mouse buttons, you’ll need to use an addon like Clique to get around it (or the new Blizz thing but it doesn’t seem to play nice with mousewheel stuff).
I played just a little with the new Click Casting. (You can open the interface by clicking the Click Casting button in the bottom left part of the Keybindings panel.)
It seems to work for mousewheel clicks. (At least for my mouse, the middle click is MB3 and the two tilts are MB4 and MB5.) It won’t let me bind mouse scrolling (MWU and MWD) but those don’t get eaten by raid frames, and so work like keyboard keys for action bar binds already.
The Blizzard Click Casting binds override, but don’t overwrite regular keybindings. Here’s how you can use that to get full use from a extra mouse buttons. You can set the binding up on your action bar with your regular mouseover macro. This will work in all situations where your mouse isn’t over a unit frame (which will eat the click.) But, you can also set that same mouse click to click cast. When you’re over a frame, it will use the click cast settings. When you aren’t, it will use your regular action bar macro.
So, as an example, I set up middle click on my action bar, with the following macro bound to it:
#showtoolip
/cast [@mouseover,help,nodead][@player]Flash Heal
It works when mousing over friendly units out in the world, but not when over a frame. So, I went into the Click Bindings, and bound Flash Heal to middle click. Now, it will cast Flash Heal both when over a frame (using the click binding) and when over a target in the world (or on myself with no mouseover target) from the keybound macro.
It’s a bit weird, and some extra work. I haven’t used Clique in years, so I don’t know if that’s a much easier solution or not. But, it looks like with some playing around, you can do quite a bit with the default setup now for those who would rather not use an addon for such things.