Sure.
and then you're firmly in autotools land
Not at all. If you need the send(2) POSIX system call, what are you going to do if autotools detects that you're on a platform which doesn't have the send(2) system call?
Still, there's relatively few portability issues these days:
1. Some platforms don't define MSG_NOSIGNAL. (You can work around this via setsockopt.)
2. Some platforms don't define CLOCK_REALTIME. (On platforms which don't provide that, you should be able to use gettimeofday.)
3. Some platforms don't understand -lrt or -lxnet. (This one is awkward since some platforms require those. You have to either taste the compiler or detect the OS.)
4. Solaris needs -lsocket and/or -lnsl for networking related functions. (Either detect Solaris or decide that it's rare enough that you don't really care about supporting it. In spiped I opt for a note in BUILDING telling people how to work around the Solaris standards-compliance bug.)
Compare this to the situation when autotools originated, and we're about 99% better.