Note that you can still register domain names that end in .COM — they're just not the default anymore, and these days you'll be lucky if your first (or second or third) choice isn't already taken.
.CO domains cost more, but they're given out and resolved the same way as domains ending in .COM, and they're already recognizable to users in some countries (the United Kingdom and Japan, for example) so they're a viable alternative if every .COM domain you want is held by either a legit company or an unmovable URL squatter.
Twitter uses a .CO extension for its URL sharing service, and shopping site Overstock.com recently launched a campaign to promote its alternative URL at "o.co." Will you be jumping on the .CO bandwagon with your next website?
Update: .CO domains were just a test, and GoDaddy has reverted back to .COM domains. But that didn't stop people from scooping up the shortened domain during the brief window when it was available.