My biggest beef with whitespace having syntactic significance is every developer wants to see different levels of indent, and every editor seems to have its own special way of writing out whitespace. They're not always compatible, and making them all work together can be a pain in the ass (for instance, emacs and vi are notorious for doing it differently, and emacs does it in a way which breaks vi).

I may want tabs at 8 spaces, you might want them at four ... someone else might want actual spaces. You can't see them, so you don't really know what's there. It fails miserably in teams where people use different editors.

That, and whitespace having syntactic significance flies in the face of context-free grammars and everything I learned in compilers. If you disagree with the "Dragon Book" by Aho, Sethi, and Ullman ... you're wrong. :-P

There's a large amount of whitespace characters, which don't all display the same in every tool -- and, in my opinion, it makes you lazy about closing actual blocks.

To me, relying on the indent level and whitespace is lazy, and something you'd have learned to do 'properly' in a Wirthian language -- where if you don't do begin/end blocks you can end up with crap code which doesn't work the way you expect.