Validate your code by testing it in the three major layout engines. Force it to degrade by disabling flash, stylesheets, javascript, etc and fix what you feel you can. Get as much content on-screen as quickly as you can, whether by using CDNs or backend caching or local storage, and know exactly what happens on your page in the first few seconds after onLoad. If you're feeling particularly generous, annotate the code for screen readers and hide jump links around your page.

But don't validate your code on the W3C validator and be done with it. If you have to run the validator at all - and I haven't in years - take the validation errors as suggestions and not as gospel.