If you're not used to distance riding take it easy at first. Commuting by bike is great, but you can burn out pretty quick if your body isn't used to 2+ hrs of daily exercise. Riding 1-3 days per week is a good goal initially. Another option I liked was split commuting. Put the bike in the car, drive in the morning, bike home, and bike in the next morning. It cuts down on the daily time impact from commuting.

The backpack really depends on what style of bike you're riding. On an upright mountain bike, a light backpack is fine for hours. On a road bike where you're leaned forward, the backpack gets uncomfortable quickly. Panniers are fine but expensive, for light loads a quality messenger bag with a secondary strap is quite good.

The biggest factor with comfort is figure out what you need to carry. Taking a 15lbs backpack to a 5 lbs pack makes a HUGE difference. Since you're not entirely car-free, can you leave items at your work place? For example, drive in on Monday with clothes for Tues/Wed? Go through you backpack and figure out what you actually NEED. When you're driving, hauling 5 lbs of extra papers, books, electronics doesn't really matter. In a back-pack you notice that immensely. The biggest thing for me was leaving my shoes at the office. I wear clipless cycling shoes, so not having to carry 3-4lbs (size 13 feet) and the extra bulk meant I could use a small messenger bag instead of a full pannier.

This is going to sound counter-inituitive, but big cushy saddles are TERRIBLE for longer distances. If she's got a big cushy saddle, see if you can't get a cheap replacement that has less padding. There's plenty of good options for ~$30 in terms of saddles. Good bike shorts can also help.