I open with a pre-ass-kicking one-liner. "You know the phrase 'speak softly and carry a big stick'? Well I'm the most soft-spoken person you'll know."
I usually don't mess around, I go for the vitals right away. Throat, solar plexus, even the temples once.
There's a weird thing about the human body where striking the trunk nerve in the armpit cripples the whole body for just a little bit. I thought it was a great load until I got the opportunity to try it, and goddam, I was just as surprised as the other guy. I didn't follow up on it, which is alright because he was too freaked out to keep going.
Of course, I've only been in a couple "fights" in my time, so take my off-handed bad-assery with a grain of salt.
In games, I go for either the counter-heavy quick stuff, or the big heavy fists, depending on my mood and the weapon.