I googled up a couple of maps, and at a very pragmatic level, I think there are a couple of very unemotional things to consider:
While keeping on a course that parallels one or more Underground Railroad paths, the new route should:
1) connect two or more existing routes
2) be within a half day's drive of several major metropolitan areas
3) be on roads that are as pleasant and rural as possible.
A sample map of UG. Routes is available at this link.http://education.ucdavis.edu/NEW/STC/lesson/socstud/railroad/Map.htm
Some obvious choices would be
1) Cairo to Chicago, IL
2) Evansville,IN to Monroville, IN (on to Detroit?)
3) Cincy to Cleveland
4) Portsmouth OH to Buffalo
5) the Susquehanna river valley.
#1 partially duplicates the great river route
#3 is underway as a rail-to-trail project
#4 partially duplicates the #3 route, although the bottom half is pure TOSRV.
#5 suffers from a lack of good roads.
If I might make a few observations about #2
a) it would connect the TransAm & Northern Tier as well as the Lake Erie connector.
b) It would serve Louisville, Indy, Cincy, Detroit, and possibly Chicago, Grand Rapids, etc. It passes near several cities, but through comparatively few.
c) Low traffic paved roads abound, (plus camping, etc)
d)In combination with the Northern Tier, an "omega" shaped route could be devised as follows: Louisville-Monroeville-Syracuse-Philadelphia-Cumberland (C&O canal path).
e) some rural (read: easy to route to) sites remain, including a "Grand Central Station" (Levi Coffin House, just north of Richmond, IN).
Thanks for reading this far :-) Is it really obvious that I live in Indiana?