I'd like to see a huge multi-part demon as a boss. Perhaps a soul stealer with his victims' souls chained to his body, magically compelled to attack you until you kill them [before you can attack his main part]. He should also have seperate points on his own body to attack: a scorpion-like tail, eyes that shoot fireballs or something...
I really like long, vicious boss fights [one of my favorites was the evil goddess at the end of Breath of Fire 3 - no fight has ever taken me that long, or made me feel that accomplished afterward].
The mythological creature suggestion is also good. But it should be with a twist. Seeing a unicorn with a forked tail, scales instead of fur, red eyes and a super-long blood-covered sharp horn would be great.
You could also make a race with snake bodies and human-esque faces. They could have 2 arms, move quickly and silently and be archers. They could even summon packs of regular snake minions to supplement their attacks. I'm thinking red and fire-orange scales, clawed fingers, pointed and writhing tails - and fire for hair!
