I've said a few things about this topic, nothing too inflammatory and nothing outside of the truth, but I've come to a realization and it's a simple one.
It doesn't matter which path you choose to get your work out, just get it out.
Others have touched on this, Chuck Wendig did a great post on it awhile back but I thought I'd add my own two cents.
I'm and independent author. I rely on no one but myself to get my stories to my readers. I hire out my editing, cover art, and formatting and I have great people who help me with these aspects that don't involve the creation of the actual words. At this point in my life it's working out great. I'm having more readers, success, and money come in than I ever thought possible and I love it. I'm in control of my content, covers, descriptions, and formatting. It's a lot of work but it's extremely gratifying to know that I can change it at the drop of the proverbial hat.
Now don't get me wrong, this isn't a bash-the-shit-out-of-the-big-six/five/whatever. It really isn't. Honestly I might even pursue a publishing opportunity with one of them someday. You know why? Because they can reach even more readers than I can by myself. They have more marketing muscle and clout than I might ever have alone. I undoubtedly will give away some of my control, but perhaps it will be an even tradeoff that I'll be willing to make. The other thing people talk about is the collapse of the publishing industry as we know it. I think that's blowing things out of proportion. I think there will be restructuring and basically a shift, but the industry will still be there in fifty years.
The point is that you need to do what works for you.
If you get rejected by a hundred agents and a thousand publishers, publish it yourself! Put it out there. Kealan Patrick Burke once said that independent publishing isn't removing the gatekeepers, readers are the greatest gatekeepers out there. You'll find out soon enough if your work is up to snuff, your readers will tell you.
If you think self publishing isn't what you want, find an agent, don't quit til' you do, keep submitting manuscripts until one sticks and you get an offer from a publisher.
In the meantime keep writing, don't wait around sitting on your thumbs while they could be hitting the spacebar over and over.