About Comair flight 5191:

Weather at Lexington-Blue Grass Airport (LEX) was fine on the morning of August 27 with a small shower approaching from the West.
It was still dark just after 06:00 as Comair flight 5191 taxied out for takeoff. The flight was cleared for a runway 22 departure, which is Lexington's main runway. Because the runway was repaved just recently with an added safety area at the approach end of runway 22, one taxiway was no longer in use. Since August 20 the taxi route to runway 22 was changed. The crew inadvertently lined up on the shorter (3500 x 75 feet) and unlit runway 26. The first officer commenced the takeoff roll. One of the pilots made a remark about the lack of runway light illumination, but the takeoff was continued. The fully laden CRJ was not able to rotate within the 3500 feet runway distance and continued past the runway end. It knocked down a metal fence and continued onto a field. The airplane struck several trees and burst into flames on a working farm.

NASA ASRS records show a possible similar scenario when some 13 years earlier a twin engine passenger jet inadvertently taxied into position on runway 26 at LEX while being cleared for an immediate runway 22 takeoff. The tower controller noticed this and cancelled the takeoff clearance. According to the report "Possible contributing factors were poor visibility and wx (rain), confusing rwy intxn and twr's request for an immediate tkof."
In the meantime work had been performed on the runways at LEX. Since October 2003 for instance a runway resurfacing project was started. The project also added 600 feet of safety area at each runway end.

Probably cause:

The flight crew's failure to use available cues and aids to identify the airplane's location on the airport surface during taxi and their failure to cross check and verify that the airplane was on the correct runway before takeoff. Contributing to this accident were the flight crew's nonpertinent conversation during taxi, which resulted in loss of positional awareness and the Federal Aviation Administration's failure to require that all runway crossings be authorized only by specific air traffic control clearances."