I'd be interested to know your thoughts on NGINX versus Apache. I prefer NGINX because NGINX is specifically designed and engineered to serve concurrent requests (lots of users connecting to your website at the same time), much more efficiently than Apache. There are some trade-offs to this (for example, you can't make configuration changes in real-time), but the results can be massive for a high-traffic website.
What's your thoughts? You can read more about it here, with a whole load of other Magento tips: http://goo.gl/bM24Eo
You have certainly asked a BIG question on the Magento Forums!
Have you read through what NGINX has to say about it?
Here are some practical considerations
One of my favorite articles from Sonassi hosting
So what is your question? How many users are you serving? How many orders per hour?
All those go into your answer. Of course many hosting companies are starting to support NGINX out of the box so again. Why wouldn't you go with it? How often are you restarting your Web server that you need to worry about changes? If you are in fact that busy why don't you already have two web servers load balanced? Then you can restart one and then restart the other later