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I have yet to have a novel published either way but from other writers I know:
Large publisher will give you the highest ceiling and higher starting point as far as sales and income go. They're more restrictive and more involved in what you write. You'll have more books, in more places but always marketed all that much. If it's your first book more than likely most of the marketing will still be up to the author.
Small Press starts with a pretty low ceiling (limited print runs, perhaps only in the 100's). Some small press authors will sell as many books as authors with larger publishers, but not often. Many small press publishers do not offer advances, but give you a higher percentage of the net sales. Most of the time you will have complete freedom in writing so long as it's in the niche that they publish in. The culture is a lot different, more like friends than having a overbearing editor breathing down your neck.
Some authors can be quite successful in with Small Press publishers. If you write in a niche and have a relatively large cult following like Brian Keene or someone like that.
There have been cases where a small press publisher has a relationship with a larger publisher. One example is Permuted Press who has a deal with Simon and Schuster. If you write horror and get published with Permuted Press, you have a chance of you book being picked up by S&S.
There are also many cases where an author started out with a small publisher and was later picked up by a major publisher.
So, I'd say that if going the route of the major publishers does not work out, go with a quality small publisher. Even a small publisher can get your work in front of the eyes of more people and increase chances of being picked up by a larger one.
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