Not at all. Portage x86 versions of xmame (0.102) and gxmame (gxmame-0.35_beta2) are fine together, and they have no problems at all with my rom collection, which is quite huge.
Hmmm, GXmame was puking when trying to make a game list. Still some leftovers when mame switched over to XML format, I thought. Perhaps I have some concurrent gxmame binaries lurking around somewhere causing problems. Anyway, like I said, the CVS of GXmame is working fine for me with xmame 0.102. I know how to set the paths. :p
You can't get much larger than my ROM collection:
doug@ghidorah ~ $ du -sc /usr/share/games/xmame/
44G /usr/share/games/xmame/