First read through, the main differences between 5th and 6th.

Psychic powers have changed, but you can optionally use the normal ones you have access to in your book. That is is you get any.   I suspect people will use the normal ones in their books for the time being in my gaming group at least.
Vehicles and power weapons are most changed.  Vehicles now have a number of hit points.  You lose one hit point on a glance, and on a penetrate you lose 1hp and roll on the death chart.  Most tanks, execept landraiders and monliths have 3 hit points, so glance, glance dead occurs.  Power weapons are now divided into four different types.  They all cost the same and have different stats. 

Random charge ranges are in though jump troops and fleet troops get rerolls on their 2d6 charge dice.  This is combined with premeasuring which should help somewhat in combating failing a charge with actual close combat troops.

All heavy weapons which are not blast or flamer can move and fire at Bs1.   This is called snap shot.  You can also snap shot as a stand and shoot reaction, flamers work here inflicting d3 hits automatically.  Rapid fire weapons like bolters can fire their 1 long range shot even if they move now, two still within 24 inches. Tanks while moving get to fire 1 gun with normal bs, but other guns have to be fired as snapshot [bs1] so twinlinked guns are where its at.  Flamer/blast weapons not being able to use snapshot will obviously need to be fired using the main BS.

All characters including sergent types get look out sir.  They also have a great rule that if the character rolls a 6 to hit with shooting or combat you choose who gets hit.
Wound allocation is now far more sensible.  Basically you make your saves and the nearest models die, no miraculous survival of heavy weapons if they are stood at the front.  There are complications due to terrain, because you can choose to just shoot those in the open, or in lesser terrain, but then you can only kill those models.  This is much better IMO.

Flyers and flying monsters have the same rules as before as well as an alternative much faster, but less manuverable method of flight.   Monsters will probably overtake dreadnoughts in importance due to the changes to tanks.  Monsters can be attacked by anti vehicle grenades, but they typically are tougher with armour/wards so shouldn't get bogged down too much.

Deployment is different.  You now choose sides, mission etc before setting terrain up to facilitate the addition of fortifications.  You can also now take allies from a list, which depends a lot on what army you play as.  A lot of alliances you would expect are in there, eg marines with each other and other imperial forces, but some are more unusual, eg marines and tau.