The pain points are what other commenters have said:
- I don't find the default config a good fit for me, and run it heavily customized. As someone said everything in Emacs turns into a project...
- Performance can be an issue, especially indexing new mail (and especially if you like to lug around a copy of most of your emails locally as I do). On a laptop while traveling this used to be more of a problem, but newer versions are notieably quicker and newer laptops have better battery life.
- HTML rendering isn't great. Thankfully I don't get too many important messages that isn't just plain text. This might be a reasonable use case for xwidget-webkit though I'd imagine there are security/privacy issues to work out. (Another Emacs project -- yay!)
When I started I thought it would be an efficient way to get through lots of emails, and it has been for the most part. I'm just not sure I've saved time overall unless one counts the hours configuring it as "entertainment / hobby" rather than "work".