As long as you're fine with web crawlers not seeing your content, people not building mashups based on your HTML, and so forth, be as much of a heartless bastard as you want. But do keep in mind that Googlebot is the biggest disabled user in the world. If blind people can't see it, search engines can't see it. And if search engines can't see your website, who cares about you?
If I want people building mashups with my site, I'll provide an API, HTML is not an API.
If I want Google to see my data, I'll provide it to them when they crawl, more accurately, if I'm ajaxing in data with JavaScript, it's usually explicitly because I don't want crawlers getting to it.
It is not a web developers job to go out of his way to support people who deliberately break their browsers and more often than not contribute very little to the bottom line. Most of us are building apps for people that actually want to use them as intended.
Hypothetically assuming I had a product targeted at people who were technically capable of developing mashups (or, for that matter, had ever heard the word), I would want to have them use a published API rather than my HTML, because I routinely need to change my HTML. I do not want to have to give everyone 6 weeks of notice every time I do a split test to avoid breaking my core users' sites.
