Do the worksheets on the W4 to figure out how many exemptions to claim. With a working spouse (even if she is in residency,) you might need to claim zero exemptions and have extra tax withheld if you want to avoid paying taxes at the end of the year.
Me, personally, I like to keep my $$$ as long as possible. I save(d -- while I was working before I had the crazy idea to go to medical school) a lot, so the potentially big tax bill at the end of the year was no big deal. You may end up paying penalties doing things this way, but I think my penalty one year was something like $100 on 6 figures of investment income on which I didn't pay estimated taxes (similar to not withholding enough.) But, if you want to "pay as you go," you can fill out the worksheets on the W-4 form (which will guide you on how to fill out the W-4 form itself.) If you do not completely understand what I am talking about (and the ramifications thereof,) or are uncomfortable with it, I woulds suggest talking to an accountant.
Personally, I think now is a great time to put $$$ into the market (buy low,) if you have the cash, but I don't claim to know the future. Don't gamble more than you can afford to lose. Nevertheless, you could still realize the tax benefits of a 401k by contributing the max (even though they can take up to 18% per paycheck, you cannot contribute more than 16.5k per person per year to your 401k -- your employer will likely cut you off if you hit that limit, but be careful because it is hard to get that money back if they over-withhold for your 401k) even if you invest your 401k into something less risky like bonds or even a money market account, if you are risk-averse. One other bit of advice about 401ks, if your wife's contributions are not percentage limited, you can have her contribute up to 16.5k per year as well. That would be a significant fraction of her stipend, but so what -- you'll just live off of your income. That would reduce your AGI by 33k, putting you well under the "now screwed by Obama" 250k+ amount.
Anyways, I ended up babbling more than I thought I would. Hopefully you'll be able to get something out of my ramblings...