Fly. Siem Reap Airways (FT, ironically) is the best bet -- they have good planes and fly the route 3-5 times a day. See
www.siemreapairways.com -- they're a subsidiary / affiliate of Bangkok Airways (PG). IIRC, fares are currently around $65-$75 one-way; roundtrip should be a little less than twice that.
For those who want to spend more time and / or less money, there are some fine buses that make the trip in around 5+ hours. Mekong Express is said by many to be the best; I haven't tried it though.
Enjoy your trip,
Michael