Users are slow to change, and buying your software through a portal on your computer is a big change.
1) Upgrade pricing. At best you'll get convoluted instructions on how you can obtain an upgraded version: http://www.barebones.com/store/bbedit_MAS_upgrade.html https://support.omnigroup.com/omnifocus-2-upgrades/
In many cases, you can't go back and forth (bought on website, bought v. 2 on MAS), so you're expecting people to understand that it's a "different" version - imagine if you had to explain that because you bought the Best Buy XBox One, you can't play games purchased at Wal-Mart.
2) Sandboxing. If users are going to pay anything near full price for something they expect full functionality.
Due to these headaches, publishers are abandoning the App Store:
http://www.panic.com/blog/coda-2-5-and-the-mac-app-store/
Personally I wish the MAS was a better solution for the reasons you described (I have purchased a good amount of software there)