Is there a way to do "mouseover" spell casting without a macro?

The only other way to do this without a macro is through the use of an addon.

Clique is probably the most well known such mod - it essentially allows you to bind spells conditionally based upon the frame which you're currently moused over.

It's extremely popular with healers.

See also @LessPop_MoreFizz's answer. What I want to do is not currently possible in the default UI without using addons. @LessPop_MoreFizz suggested the Clique addon.

Clique supports just mouseover quite easily. However, I want my buttons to cast on either my mouseover or, if I am not mousing over anyone, my target. This is a bit harder to do for some reason! (Maybe I should talk to the author or add it.)

Once again, my intention is to replace this macro:

/cast [@mouseover,help][] SPELL_NAME

Where SPELL_NAME is "Penance" or "Heal" or whatever.

Here is exactly how I set it up. I used Clique version v40000-1.3.2.

1. Install Clique and sign into WoW.
2. Open up your Spellbook.
3. Click on the "Clique binding configuration" tab on the right.
4. On the bottom of the Clique pane, click "Bind Other" -> "Run Custom Macro."
5. Set the keybinding by hovering over the button and pressing a key. For example, I use 1 for Heal.
6. In the box below, type /cast [@mouseover,help][] SPELL_NAME.
7. Save. You should see your custom macro in the list.
8. Right click on it and select "Enable/Disable binding sets" -> "Global bindings (no target)"
9. Repeat steps 3-8 for all spells you want controlled via Clique.
10. Done!

You could, if you want, leave your action bars empty at this point. Clique is totally handling the keypresses for you and you don't need the buttons. However, I replaced the buttons in my action bars with the regular spells by themselves instead of the macro versions. This allows me to see the icon art with keyboard bindings (in case I forget which button is for a spell), cooldown counts, range indicators, tooltips and such. Though, note that those action bar buttons are mainly artistic - when you press the key associated with the button, you are not actually pressing that button because Clique is intercepting the keypress and doing its own thing instead.

The downsides to this method:

• It's not easy to set up Alt+1 commands to cast a spell on yourself without another round of custom macros. Ugh. Though just hitting the key with no target and no mouseover casts on yourself by default anyway.
• It's a little hard to maintain; if I want to move a spell from one key to another, I need to update Clique and I want to update my action bars as well (though again, the action bar part is just so I can see the spell icons & keybindings, cooldowns, range indicators, and tooltips).
• Doesn't transfer to other machines automatically like macros do.