While I’m not able to comment on resets (not knowing what they do) I’m not a fan of pixel-perfect or fixed designs. I like designs that behave nicely when I resize my browser (small columns do not count as nicely - use the whole real estate I have!) and when I change my font size settings.

I do agree, however, that you can’t trust browser defaults. This box I’m typing in, for example, has almost illegible text since the foreground colour has been set to dark gray, but my browser default background is black. This is common enough that I may just write a Greasemonkey script to fix it.