A different perspective from networking... I'm in the accounting field and spent about 15 months at home after our first was born. I started looking for a job in late 2009/early 2010. If you recall, it was not a good time to look for a job. But I did okay.
Here is what I suggest- leverage placement firms (aka recruiters) and be willing to take temp/contract work. Robert Half is a big one, and depending on the type of work your wife does, she might have better luck in their Accountemps division. Kforce, Solomon Edwards, Ranstad... there are a lot of them. I know of more but they may be regional. The contract work may pay a little less, but the idea is you take the temporary work, continue to look for a permanent position, and when she interviews she says something along the lines of "I took off to stay home for a while, but I knew I wanted to go back, so I have been doing some contract work to keep my skills current."
I know of several people that have taken contract work only to be hired on permanently down the road. I also know people that end up liking the contract work (often the postions are laid out so you are a w-2 employee for the staffing firm- no tax headache of actual contract work...) and just like to go from contract to contract, trying out different organizations for 6 months at a time. Benefits working for a staffing firm suck, but it's something, and it shows potential permanent hiring managers that you are suitable for work.
Online, have her answer ads that look generic as well as those that disclose a lot- she probably could get in touch with some recruiters this way. I really like working with recruiters, you tell them exactly what you want and they are out there trying to make a match for you. The employers often get crap resumes through the usual avenues (monster, career builder, etc), and they end up relying on a recruiter. Sure, it comes with a hefty price tag for the employer (about 20% of your salary typically), but that is coming out of their pocket, not yours.
Good luck to her!