Some of them do have historical roots. For example, Canadian was CP because one of the components in the merger that created it was Canadian Pacific.

Others have less obvious explanations. For example, AirTran is FL because their hub used to be in Florida. Comair's OH, well, even if it's technically in Kentucky... And Varig's RG comes out of the middle of the name, while a first-and-lass pattern gives you BD for British Midland.

Most of the others, though, do seem to be without pattern. Just that all the good ones were taken. (I think they may all be taken now--new ones usually include a number, and there is a move afoot to three-character codes.)