Layout performance is the biggest problem probably - when things change the browser too often does a full layout of the document. We use tons of CSS containment but there are still bugs where Chrome does far more layout than necessary, e.g.: https://bugs.chromium.org/p/chromium/issues/detail?id=667370

Virtual DOM is completely unnecessary to us. We have minimal problems with DOM calls. It is all to do with layout performance, and VDOM makes no difference at all there.