The Demon Hunter's Chakram flies in a pattern out from her in a wide area of effect, but it circles around a bit and crosses its own path several times.
Is it possible for a single Chakram to inflict its damage multiple times to the same enemy?
Yes, it is indeed possible. Take a look at this video. The Demon Hunter's Chakram clearly hits the Skeletal Archer twice, before obliterating it.
Look like I was mistaken. Upon further investigation of the Leoric (he has a fairly large hitbox) fight, it looks like the Chakram only hits once per target.
I was not sure about the answer, though I did play the Demon Hunter. Went on Diablo III forum and found this.
According to this post, not only can it hit an enemy more then once, but that makes it one of the best DPS the game at the moment.
But yes, it's not that easy to land!