If innovation is becoming easier and easier due to the global availability of technology, and allot of it legitimately free technology, and it is increasingly easier to get the word out about your innovation due to social marketing and the viral nature of the web if your story is a good one, then one would have to assume that the only barrier left is a good idea and the crazy no holds barred pursuit of it. Sounds like an entrepreneur to me. Now if this is true the large company that can't maintain it's founding entrepreneurial culture of innovation actually has bigger barriers to overcome then the start-up. I think it is fairly safe to assume that the bigger a place gets the more and more the Peter Principle takes over and the 9 to 5ers settle in. The playing field may now be tipped in favor of the girl in the garage versus the large organization.
Therefore; size, profitability and market share may no longer be worth the valuation points that we have historically given them. They may be markers of past performance and not indicators of future achievements. The more important marker, or the one that should be given greater weighting, may be innovation (what's cooking) and market share momentum (how fast are you gaining a slice of your audience) versus the other guys.
I think the frequency by which those who dominate a market and get replaced by an up and comer will only increase over-time. If your looking for employment or a place to invest in you may want to think twice about going for the big staid company for the security. It may not be so secure after-all.