I think this is the way to forward, we may need to fix some .pc files however.

Tried to build a bit with this, changing some templates to use pkgconf and building cross, focusing on qt5 as it's known to be problematic.

I've found a bunch of templates building just fine:

• sddm (cmake)
• supercollider (cmake)
• retroarch (configure)
• abGate (gnu-makefile)
• modrana (gnu-makefile)
• musescore (gnu-makefile)
• smplayer (gnu-makefile)
• recoll (meson)
• OpenLP (python3-module)
• ReText (python3-module)
• qutebrowser (python3-module)
• gpsd (scons)
• trident-networkmgr (qmake)
• vmap (qmake)

Some failed due to unrelated reasons:

• gmic (can't find gimp, needs updating)
• uim (tries to execute a binary it had just built, should be marked nocross — also not in repos for aarch64)

Some fail trying to run a binary from wrong prefix:

• vlc (gnu-configure, tries to run qt5's moc / lrelease / etc.)
• zbar (gnu-configure, tries to run glib-genmarshal for the target machine)
• Carla (worked when I switched it to use qt6 instead)

/usr/lib/pkgconfig/glib-2.0.pc:

prefix=/usr
bindir=${prefix}/bin
datadir=${prefix}/share
includedir=${prefix}/include
libdir=${prefix}/lib64

glib_genmarshal=${bindir}/glib-genmarshal
gobject_query=${bindir}/gobject-query
glib_mkenums=${bindir}/glib-mkenums

With "export PKG_CONFIG_FDO_SYSROOT_RULES=1" added to the wrapper via common/hooks/pre-configure/02-script-wrapper.sh, vlc and zbar both built fine

This indeed breaks the default pkgconf behavior, but I also tested the templates that already have pkgconf defined in requirements, and everything except libportal, as discussed here worked.
To toggle between the two something like..

if [ -z "PKGCONF_SYSROOT_RULES" ]; then
    export PKG_CONFIG_FDO_SYSROOT_RULES=1;
fi

..might make sense in the pkg-config wrapper, so it's defaulting to the old behavior (that should be compatible with almost all templates)

Most notable, though, was the build failure of libreoffice.
It fails with both: pkgconf (as-is) and pkgconf (emulating pkg-config sysroot rules), with the same error:

checking for CLucene/analysis/cjk/CJKAnalyzer.h... no
configure: error: Your version of libclucene has contribs-lib missing.

But it works with pkg-config (as used currently).
Perhaps it'd be nice to retain the ability to switch a template to use one over the other if absolutely necessary.