D2D and Smashwords are good solutions for markets you can't get into on your own. You'll want to go direct everywhere you can, because the odds are you'll have more sales that way, and you will definitely earn more money that way.
Amazon is a no-brainer--just go direct. Invest the time to figure out how to publish there on your own. Unless you plan to only publish one or two things for some reason and don't want to bother, in which case pay someone to do it for you once, don't pay 15% perpetually to go through a service like Smash or D2D.
B&N through Nook Press--if your'e in the US, go direct. All the same reasons. The one exception would be that if you want to eventually make something permanently free. Then go through Smashwords, which is the only outlet i know of that will let you change a book's price to free on B&N. Lulu might, but I'm not sure they will, and uploading something through Lulu seems unreasonably complicated compared to Smashwords anyway.
Kobo through Kobo Writing Life--go direct here for all the same reasons.
Apple through either Smashwords or Draft2Digital--here's where the real benefit is. I'd recommend Draft2Digital for Apple. It'll probably show up faster, if it's rejected they'll tell you why (Smash doesn't bother) and your price changes go through quickly, all benefits over the way Smash does it. You can go direct with Apple, but you have to jump through a lot of hoops and using pen names isn't allowed unless you have appropriate DBAs for each one. You have to have a Mac, pay for Mac in the Cloud or get someone with those to do everything for you. Apple through D2D is much simpler.
Those are the biggees. If it's romance, go direct through AllRomanceEbooks. You can also upload to Smashwords if you want to get in places like Sony and Diesel stores and to sell on their site directly. The Channel manager lets you pick and choose.
I upload to Smashwords to sell on their site-no premium distribution with the exception of one title I wanted free on B&N. I use D2D solely for Apple. I go direct with everything else. The benefits go beyond not having to pay someone else. You have more control when you go direct, you can change things more quickly, and you can control your metadata better. I didn't sell a single copy on Kobo in over 6 months. As soon as I went direct I started selling copies there. When I went direct with B&N, I more than tripled sales. Many stories echo mine.
If you can't be bothered to read the instructions to upload direct, pay a service that will do it for you once and leave you in control. Don't pay someone a chunk forever when you don't have to.