First, a lot depends on your flight habits and plans. Yes, if you have a choice of airlines with reasonably equal schedules and prices, it's best to focus your travel on a single airline or alliance. Keep in mind though that what you can get is still limited. Even if you fly from LAX to Italy, it's still only about 12,000 miles round-trip, which at best will be half of a domestic round-trip ticket or an eighth of an international business-class ticket.

For people who aren't road warriors, the best deals are credit card bonuses and points. I know you said you're not interested, but that's where the points are these days.

Forget about upgrades. In practice, getting upgrades with points usually require a fair amount of points, and often also require you to buy a somewhat expensive fare. Upgrades are usually the province of elite fliers (i.e. those who fly at least 25,000 miles a year on a particular airline/alliance, and often 50-75,000 miles a year are required). There is also no such thing as a "reduced-price" flight, although when you consider that taxes, fees, and fuel surcharges can run into the hundreds, maybe a "free" ticket (notice that airlines no longer call them "free" they call them "awards") is really just a reduced-price ticket.

The best "deal" for your points is international premium class travel. If you just look at the posted prices, a round-trip business class ticket to Europe can easily run $5,000 or more, while you can sometimes get it for 100,000 points, or a value per point of 5 cents. Most of the time, though, you be doing quite well to get rewards of as much as 2 cents per point.

I would just pick an airline that you think goes most of the places you want to go, and try to travel as much on that airline or its partners as you can. It doesn't cost anything to sign up with other programs, but keep in mind that you will need 25,000 points to get anything of value (except sometimes gift cards that won't be a very good value for your points) and if you only take a trip on a given airline every few years, it's really kind of a waste. Many airlines have points that expire anyway. I got a couple thousand American Airlines points for a flight I took two years ago, but I didn't fly them again and they expired. No great loss.