It is worth noting that currently a Tupfile can create files in a different directory. You could always read files from different directory, so currently you can have a single Tupfile for the whole project.
Some more info here: https://groups.google.com/d/msg/tup-users/h7B1YzdgCag/qsOpBs4DIQ8J (a little outdated) + https://groups.google.com/d/msg/tup-users/-w932WkPBkw/7ckmHJ9WUCEJ (new syntax to use the group as input)
If you use the new LUA parser you can also have a "default" Tupfile - see here http://gittup.org/tup/lua_parser.html and check info about Tupdefault.lua