Despite the fact that we love the Vash/Meryl pairing... yes, there are a few possible problems with it. (Well, arguments against it, at least.) However... I think all of these apply to any relationship Vash would have. Of course, I also wasn't thinking too intently on the subject. If you have any other things that are wrong with it, e-mail us?

Ménage à Trois
The Rem thing. Really, this is such a big part of any relationship Vash would have, it's got its own section: many waters

The Shyness Aspect
Vash doesn't seem to much care for being physical — more of a modesty, perhaps. Well, whatever it is, the boy has major issues. Much as he chases girls around all over the place, he's never really serious about it. This is perhaps partly because of his arms and because of his many, many scars. Meryl, of course, seems to accept this—but I'm not sure how Vash himself would be able to get over it. Then again, the more I think about it, the more I think that might not be a problem; though Vash initially seems uncomfortable about it, I'm not sure it's something he'd really dwell on. Ah, how contradictory I am.

That Whole Non-Aging/Non-Human Thing
Okay. So Meryl is going to get old, and Vash, as it currently appears, is not. This is going to cause a serious problem in any long-term relationship Vash would be in. It probably also prevents him from getting serious about anyone. This is the main problem I see in the relationship—and I'm not sure how exactly to get past it except to horribly paraphrase V.C. Andrews: "I'm not asking you to love me forever. Just love me as long as you can." That and, well, miracles happen. You never know. This is anime, after all.