Sensor size and lens quality — the Nikon D800/D800E and its higher resolution Nikon and Canon successors along with the Zeiss UP lenses (55/1.4 for starters) will make the Leica S and its brethren almost superfluous in the market, putting a world of hurt to not just Leica, but other medium format vendors. Sensor technology coupled with world-class lenses means that 36 X 24m is plenty big for 99.99% of even the pros out there. The 36 X 24mm sensor size should be able to support up to ~60 megapixel imagery with the upcoming lenses. It won’t be cheap, but it will be a LOT cheaper than the medium format game.
Quality vs size — Size wins (smaller is better)— in 99.9% of the market volume. So when quality rises to a very high level at small size (think Sony RX100 as the existence proof), the lifeblood of DSLRs and other contraptions is vampired away. This is one reason I say that Nikon DX and Canon EF-S are stone-cold dead; they have no reason to exist, being excellent at exactly nothing. It is the same reason that full-frame DSLRs will starve the medium format market.
Lens quality — in the DSLR market, the lenses designed to be good enough for film just don’t cut it. We will continue to see a rise in lens prices for premium lenses, because making lenses good enough for 36+ megapixels is hard, it demands much more expensive designs and glass types. Olympus has already proven (to me at least) that the expensive SHG lenses are the ticket— but they are huge and heavy and not cheap, though much less expensive than Leica glass and better and far more versatile on smaller sensors such as MFT. The Micro Four Thirds sensors are not good enough yet to be fully satisfied, but that should come in 2-3 years.
Focusing — Get it right already. Focusing is now the #1 issue in sharpness. Canon has made progress here, but I remain dubious about Nikon’s ability to get it right, either with the ridiculously degraded Live View functionality of the D800, or with autofocus error. Total disconnect (engineering failure) between camera resolution and focusing resolution. Not that one cannot work around such things, but this is absurd given the technological advances in resolution.
Video — this is here to stay. And after using the Olympus OMD E-M5, I am persuaded that video can be useful without being a chore. Though I want 4K video— even good HD video shows clear limits on a high-res computer display. No DSLR can yet offer the ease of use of the E-M5 for video; all DSLRs are abysmal failures for my purposes in outdoor use where I’m going to follow focus or carry a “rig”.