It only matters if you intend (or require) to CNAME your main site off to some other DNS name. If you're serving your entire site from S3 for example, you can't just alias yoursite.com to your-bucket.s3.amazonaws.com, but you can CNAME www.yoursite.com and have a small server sitting on yoursite.com sending a 301 redirect for every request.

Github and Twitter are large enough to not care. And if you're using something like Cloudflare, they can just take over your IP address with BGP, no DNS trickery needed.

I've worked a sysadmin for more than 10 years now, and never realized that it's not possible to CNAME the domain root. It's good to keep in mind, but in most cases there are other workarounds.

This is also why "naked domains" set up a whole other domain for static files rather than "static.yoursite.com", to avoid the "top-level" cookie (megacookie?) being sent with every request.