Replacing Makefiles isn't the hard part. People do it all the time.
The hard part is figuring out a migration path away from Autotools. Not even replacing them, that's relatively easy. Integrating them into a world dominated by Autotools, that's difficult.
Hm. At first glance this doesn't seem too bad: idiomatic autotools usage involves files that are relatively easy to parse and are also relatively declarative, so making a non-autotools buildsystem that's capable of directly reading configure.ac and Makefile.am files seems doable.
Why doesn't this work in practice? Non-idiomatic usage? Custom autoconf scripts?
The hard part is figuring out a migration path away from Autotools. Not even replacing them, that's relatively easy. Integrating them into a world dominated by Autotools, that's difficult.