I have done it a few times on my own large mega-merger amalgamation of multiple routes. The total length is about 190 miles end to end, not counting side routes, branches, and yards. The trip took well over 8 hours and I found myself nodding off in places. In the end I decided it wasn't worth it and let the AI do the boring driving of the long distance stuff and I stick to the switching and fiddling around. The puzzle of pulling various freight cars out of a yard and sorting them so they get to their destination without impacting the hotshot freights and varnish can be a challenge in its self and quite a time eater as well. In the length of time I spent driving the 190 miles, I tied up the mainline a few times, delivered boxcar loads of goods, pulled a bunch of coal hoppers on a mine branch, and interchanged freight with a through running manifest. That operation too is interesting. You need to cut the engines off, direct the AI to drive to the engine terminal, wait and x-amount of time there, and then switch in and out any freight needed to complete the run. Once the switching is done, the AI is directed back on to the point and told to continue the schedule.