The best way to get significant numbers of points is by credit card signup bonuses. Most cards have bonuses of 40-50 thousand. Some have tricks and catches, for example, the United Explorer card appears to give more points if you have miles in your United account. So open a Mileage Plus account, sign up for their dining program, go eat at one restaurant, then you have miles in your account.

Overseas premium class cabin travel can be fun (will your wife mind? I assume not) and the only way its afforbable is with points, but a lot of carriers have hefty fuel surcharges now.

One challenge can be getting enough points on a single airline for an aspirational trip. If you really want to go for the gusto, you might try getting a USA-based Aeroplan (Air Canada) Mastercard, and a few American Express cards. Aeroplan has a "mini-around-the-world" trip where I know people who've gone around the world in business for as little as 135K miles or first for 185K. (It's not easy to figure out, and Aeroplan won't tell you how, but there is a primer on it on the Air Canada board.)

If you are just looking to do one trip and are flexible on dates, it probably doesn't matter that much which airline or alliance you target, as all airlines will more or less get you from here to there if you're flexible enough.

It would help a lot if you were clearer about your travel plans. i know you may not have any fixed idea, but give an idea of some things you'd enjoy.