Thought I'd jump into this thread with some thoughts and experiences of my own.
About a year or so ago, I published the first book in my sci-fi saga, The Honour of the Knights, and have successfully had it shelved in branches of Waterstone's in England (about 12 branches).
Some stores sell through nicely (of the 1 or 2 they buy in). Others have, sadly, been sitting on the shelf since they were brought in. Still, the sales are still happening on Amazon and other online stores, and Waterstone's are buying in.
Recently, I attended Eastercon 2010 in London and met a major publisher there. I told them about my books and what I'd done and they asked me to post them to them. Yep - they wanted to read my self published POD novel.
Sadly, this morning they came back with a rejection, but I never truly expected them to do otherwise. They say they enjoyed reading it and thought the characters were well developed, but there wasn't much place for it on their list.
So, what am I doing now? I'm actually finishing up a total re-write of the first book, since it doesn't marry up with a major style change I made during the writing of the second. I'm also working in tweaks based on the feedback I've received from the POD version.
I'm planning to approach the agents again with the rewrite and seeing how that works out. Likely I'll mention the reception of the first and that several branches of Waterstone's have been happy to stock and sell it... but, we'll see what happens. I think the key to agent interest will be that the book has been quite well received, but has also been re-written.
In my humble opinion, whilst the first edition of Knights was great for a self pubbed novel, it's quality is below what would be expected of commercial standards. So that's another reason the rewrite has happened.
And I'm also FAR happier with the rewrite than the first edition. It's clearly a much stronger novel.
But we'll see.