I'd wager focus has more to do with it than size.
If you're an engineer, it's a bad idea to join a start-up if their focus doesn't align with your interests. Even if there is significant equity and a great salary (it's not uncommon for funded start-ups to pay more than big companies), it's terrible to feel underused, unfulfilled and behind the technology curve in the topics that interest you. If you're the _only_ person knowledgeable about a certain topic in a start-up, there's nothing you can learn about it from coworkers. If one is uncertain of their focus, there's also no ability to switch groups and work on something else.
Your start-up (OpenDNS) is fairly unique in San Francisco, if not Bay Area as a whole, in being focused on network infrastructure (and I applaud you for it, it's a great service!)
Unfortunately, it (+ several other start-ups e.g., rethinkdb) is an exception, not the rule. The focus of most other early stage start-ups is web development. Engineers interested in solving other kinds of problems (e.g., algorithms and scalability challenges) but who like the flexibility of working for an Internet (vs. shrink-wrap product) company typically consider the medium (Facebook, LinkedIn) and big players (Google, Yahoo, Amazon).