Blimpie, Yes, ATC is "supposed" to make sure that the airplane that they cleared to taxi, take-off, or whatever they assigned for them to do are in fact doing it. Also, air carrier operators such as Comair, Delta etc. have different air-crews going in and out of , often times, unfamiliar airports. For that reason the FAA produces Airport Facility Directories (AFD's) which give Taxiway and Airport digrams. My guess would be that the winds were out of the southwest yesterday at LEX, so runways 22 and 26 would've been in use, and the tower would have had a clear view of both. Runway 22 was likely the assigned runway. It's very possible that the pilot came upon Runway 26 and thought that was Runway 22 instead. This is where it falls on the ATC folks. Before they actually give that aircraft clearance to takeoff, it was on them to make sure Comair 5191 was at the correct runway.
It's a two-way deal in situations like this. ATC issues instructions and the pilots read back the ATC's instructions for ATC to verify that the pilots do understand the instructions as given by ATC. Also, if a pilot becomes confused in an unfamiliar airport, ATC is more than willing to give "progressive taxi" to a pilot, meaning that they will give them turn by turn instructions to get them to their assigned runway, taxiway, or terminal parking area/gate. I've attached an airport diagram of Lexington to illustrate. It really isn't a hard airport to get around at.