I don't think we should worry about supporting mixed 32- and 64-bit off_t. All sane programs will use plain 64-bit off_t on modern platforms. Libraries should be built in 64-bit mode as well. If you really need a 32-bit off_t library for some strange reason, build it separately; that's easy to do.
People who want to spend time building libraries that support both 32- and 64-bit off_t simultaneously are obviously free to do so, but I wouldn't make Autoconf any more complicated than it already is to help them maintain their chimeras.
