These changes have been discussed and approved by UI leads. Add your own suggestions and/or arguments for/against any items in the comments.
Continuous Grab: ON
This makes it possible to freely drag number values even if the value is close to the edge of the screen.
Also fixes issues with the number fields where they exponentially loose precision the more you drag them.
(This was previously left off by default because of an issue with Wacom tablets on OSX that is now fixed.)
Save Versions: 1
Having both .blend1 and .blend2 is a bit much when we also have autosave.
Auto Save Timer: 2mins (down from 5)
Cursor Depth: ON
More intuitive to have 3D cursor snap to surface under mouse and more useful for placing objects.
Ask to Save: ON
This is a Windows only feature, but should be enabled. It's on for OS X but quitting from the File Menu does not ask. Linux does not yet have the feature. Added task here: T37602
Mesh Option: Double Sided - OFF
Double sided geometry causes significant slow downs on most Nvidia machines, due to a bug in their driver. Until this is fixed by Nvidia double sided off gives much greater performance.
These changes have been discussed and the decision has been made to leave as is.
Auto Perspective: ON
Most of the time when switching to a side view or top view, you'd want it to be orthogonal.
Guessing perspective/ortho for the user can be problematic especially when mixing camera switching and axis-snapping, its not always possible to make a good guess, so better keep behavior deterministic & pradictable. See: T40153
Anti-Aliasing in the 3D View improves visual clarity, and is calmer to look at for long periods of time. This is very slow on some systems rB44fe9fe17b51ec5a613ad73829efb8324f73a18e
Region Overlap: ON - the current implementation is too slow
This means that the content of views don't move around when you enable Tool (T-key) or Region (N-key) panels.
Python Tooltips: OFF - these are used by both developers and artists alike, and also essential for riggers working with drivers.
Python tooltips can be distracting for users that do not need them. But this would also force many people that do use them (approx 16% according to @Andrew Price (andrewprice)'s survey) to re-enable them. Needs more discussion and waits on improvements from T37478 before determining.
Allow Negative Frames: ON - this can cause problem with audio sync.
Proposed below, but we don't really know the pros/cons, need feedback from animation module team.
Rotate Around Selection: ON - the current method causes problems when working with large scenes and many people find it to be quite annoying.
Makes view rotation focus on selected objects.