It's hard to fight efficiently using mostly the mouse. I'd press the number key of the ability and then click your target or just press enter to confirm it. I understand this may be different than other MMOs, but it's how I do it. The confirmation comes in handy for fights with multiple targets.

The absolute fastest way to cast a spell on your selected target is to create a macro for it. For example, the following will cast Fire on your target as soon as it is activated.

/ac "Fire" <t>

The quotes and capitalization are essential, or it won't work.