I think the main point nowadays is how to write Makefiles for highly parallel builds. It's surely the thing that gave me the most headaches. In the end such a talk will probably mostly be about how to avoid calling Make recursively. Another talk I'd like to hear, which would be more meta: does it still make sense to bother with Make at all, aside from maintaining legacy systems? Are there features or paradigms which still make it worthwhile, compared to other popular build systems?