I compared this pack to the Camelbak Mule NV pack and chose this pack for its ventilation and its size.
I tried on both this and the Mule NV and felt that North Face's X-vent system might ventilate better, if only a little. I didn't get a chance to run or ride with the NV but after a few rides I am very happy with the ventilation of this pack. I'm a pretty serious sweater and never stay completely dry whether I'm wearing a backpack or not, but this pack helps the sweat evaporate and keeps me cool much better than my previous Camelbak without the NV system.
Also I wanted a pack small enough to use for biking and running but large enough for day hikes. The Megamouth specs say that it has twice the volume but it doesn't seem that much bulkier than the Mule NV. And the Megamouth's compression straps can keep it compact and close to your back or expand to allow plenty of cargo space.
As for comfort; while biking the pack is very comfortable on my back. But when running or doing anything while upright the bottom frame of the pack puts some pressure on my lower back. On longer and full day hikes I think the pressure from the frame would most likely become painful. But I cannot say for sure because I haven't used it on anything other than rides and short runs. Once I take it on a hike I will update my review.
I also really like the magnet on the hose, and the Nalgene Bladder has worked well for me so far, but I make sure to close the lid very tightly. Overall, I recommend this pack to anyone looking for cargo space and ventilation especially on long bike rides.