I also like long routes which are interesting to run, otherwise, I fall asleep in the cab which has happened more than once. I took Dermmy's East Kentucky, merged that with Dave Snow's Ozark Valley and Cotton Belt routes, then added in three two more routes by Jointed Rail, MSG Sapper, and finally Dermmy's Evansville at the end. With multiple portals and AI trains running, the route gets pretty busy as I switch and run the coal trains, commuter rail, or another long manifest freight myself.
Now, I've had this route running okay in TS12, and not so well in T:ANE. It loads up fine in T:ANE, but then there are consist loading timeouts and other weird things happening. As time goes on, the signals stop working, perhaps after an hour of operation. The AI will sit at a red signal that displays a message stating no train approaching. Pressing pause and waiting a few seconds will get the script going again. This was never an issue with TS12. I have rationalized down some of the signals as I thought there were maybe too many signals, but that didn't help.
Anyway long routes are great but just use caution with the number of consists, which are sadly needed otherwise you'll be driving for hours without seeing anything.
John