I've blown my proverbial load on Enterprise, and while I appreciate the money to be made, I've found that my psyche is more suited to 100 small wins than one win worth 100x the others. In short, enterprise isn't for me, at least, not if I'm involved in the sales process. The sheer arbitrary-ness of it was so mentally exhausting that it affected my productivity.

I can work on enterprise software, but if I'm in any way involved with the sales channel, it's a hardship.

For me, the happy middle ground is vanilla B2B, e.g., the same general demographic that 37Signals sells to. You still have customers that want to pay you money, but while cost is a factor, it isn't usually the driving factor -- there's likely little difference between $25 a month and $125 a month, assuming you're solving a problem that isn't cost-centric, and you're saved from the mental turmoil of enterprise whale-hunting.