I took a look at a diagram of the airport (aerial photo, actually), and it's pretty easy to see how it could've happened. Blue Grass Airport has two runways, 4-22 (7000') and 8-26 (3500'). (Runway numbers are based on compass directions. Add a zero to the end of the runway number, and you get it's approximate direction, i.e., rwy 22 points approximately 220°. That's why there are two numbers, since you can go down them in either direction.) The two runways are arranged in almost in a V-shape, with the ends in close proximity to each other. In fact, in order to taxi to the end of runway 22, a plane has to cross the threshold of runway 26. They turned at the first runway they came to, instead of the correct one. This does not excuse the cluelessness of it all. It was dark, but runways are marked with lighted signs. There would have been plenty of other clues, too. The compass and HSI would be off by 45° or so. Rwy 26 is half the width of 22, 75' vs 150'. Finally, the runway lights for 26 apparently weren't even turned on. That should've been one heck of a clue that they were at the wrong threshold.
Meanwhile, the tower is supposed to visually ascertain that the plane is at the correct runway before giving permission for takeoff. The problem here appears to be that the thresholds are very close together, and are in approximately the same direction from the tower. And it was pre-dawn, which plays merry hell with depth perception. Again, not an excuse, but certainly it seems there was an easy opportunity to get it wrong.
A CRJ-100 needs about 5000' to get off the ground. It probably needs even more than that to stop once it gets moving down the runway. Rwy 26 was too short for either.
MLB.com even had a story about the crash, because one of the passengers was once drafted by the Indians. It's a very sad story. Jon Hooker and his wife were married Saturday, and were leaving on their honeymoon. However, I am totally going to hell because the most notable thing in the story for me was that the wife's name was Scarlett Parsley. I mean, who names their kid that?
eta: And thanks to stephl for pointing out that Scarlett's married name would've been even worse.