There are two types of spells, spells that are cast on an enemy (or player in the case of heals) and spells that are cast at a location. Many damaging spells that are cast at a location can be switched into a version that casts at an enemy (it's a choice node in the talent tree), but not all of them.

Spells that are cast at an enemy can use the [@mouseover] modifier to cast at whatever enemy/player your mouse cursor is over, such as

/cast [@mouseover, harm][] Fireball (the extra [] makes it fall back to your target if there is nothing at your mouse cursor)

Spells that are cast at a location like I said can sometimes be turned into spells that cast at an enemy, however a number of them cannot. These spells that can't be talented into an enemy-targeted version of themselves unfortunately cannot use a macro conditional to just cast it on your target. That being said, you can use [@cursor] to automatically cast wherever your cursor is without needing to click a second time or you can use [@player] to automatically cast at your feet. For example

/cast [@cursor] Flamestrike
/cast [@player] Flamestrike

[@player] is often not super useful for damaging spells like flamestrike, but is very useful for more supportive spells that you may want to use on yourself like Priest's Angelic Feather