-Use EFI instead of BIOS. It will happen eventually, go ahead and set the bar high.
-Put 8gb of bootable flash storage directly on the board. With the built-in storage put a mini-os that allows for complete control over system hardware. You should be able to overclock as well as burn-in/test settings from with in the micro-os. Allow a full OS to be installed to a separate partition of the flash. Some people do not need or want internal hard drives, they prefer NAS or cloud computing.
-Fans should be controlled completely by the EFI and tuned in the micro-os to intelligently control there speed and noise. Add a microphone to measure the db of the system while your at it. Plenty of options exist to control fan speed based off of temp. but what about a blend of temp. and noise? Again I do not want to this in the main OS.
-Fan headers could be removed and/or complimented by a breakout board with 3-pin extension cables so that fan wires were not all over the place.
-LEDs on the board, with battery backup, that illuminate certain/all of the board when swapping parts. For those that like cases with windows the LEDs should be at least tri-color and by default emit either white or red light when the case is opened. They could also be controlled by the user in the micro-os. Ex. At idle the system would emit cool-blue tones and as it warms up under load phase to warm-red tones. The lights could also use the microphone to change colors as the system got louder.
-Eliminate all legacy ports & unnecessary slots. Fire-wire, eSATA, PS2, serial, ide, PCIx1, floppy, etc.
-Full speed PCIx16 3.0, up to 6 based on board size. In most cases 4 spaced for dual-slot cards is plenty.
-Headers, SATA, audio, etc., should be mounted at a right-angle on the edges of the board. There is no reason they need to block airflow and clutter the case by sticking straight up.
-Sata ports should not be stacked when they are at a right-angle.
-Put 2 sata ports on the top-right of the board for DVD/Blu-ray drives.
-Get rid of the traditional headers for power, hd, reset, etc. Create some type of locking mechanism that will convert traditional plugs in case into something that can be quickly attached with out the fear of bumping a connection loose.