Apparently, setting USE=x86 in make.conf on amd64 arch can have funny consequences such as [1]. And I can imagine even more subtle and hard to detect errors due to this.
I think it's better to prevent this rather than waste time with bug reports like that. I asked Zac on IRC whether portage could filter such flags. He suggested using use.mask in profiles. Well since ARCH is also set by a profile, why not. Although a really persistent and stupid user could use.unmask, it's better than no protection. And then we can think how to replace the current ARCH->USE flag system with e.g. USE_EXPAND. What do you think? Vlastimil [1] http://bugs.gentoo.org/show_bug.cgi?id=236801
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