I recently discovered org-mode. Honestly, it is by far the best note-taking application I've ever used, especially in any math-heavy field, since it supports cross-references and most math symbols. And unlike LaTeX which ends up filled with markup, org stays very clean. However the basic export (to HTML and pdf) is not that good.
There's also support for basic spreadsheeting, but it gets very slow as soon as you have more than a couple hundred rows with auto-computed column values.
"However the basic export (to HTML and pdf) is not that good."
What are you referring to here? It's easy enough to customize the export formatting to whatever you want it to be, e.g., change LaTeX document class, switch to xetex for better font support, etc.
What kind of shortcuts? Most LaTeX symbols will be replaced with their unicode counterpart, eg. \theta will become θ inline, once you toggle `entitiespretty' with C-c C-x \. Likewise for superscript and index, it changes as you type.
My equation blocks are created with M-o M-s which centers the current line in the buffer (when in fill-mode), so no need for C-c C-e equation.
There's also support for basic spreadsheeting, but it gets very slow as soon as you have more than a couple hundred rows with auto-computed column values.
Sample look and feel of one of my notebooks: http://i.imgur.com/SZTxQ6v.png