Google is at least as interested as you are in having your ads perform well on your site. And they've gone to some work to provide the information you need to optimize your AdSense.
What's fascinating to me is that apparently not everyone bothers to read their tips. And even some that do, fail to apply it.
That said, you need to be aware that simply using their tips doesn't guarantee successful ads and decent CTR (Click Through Rate). How many times have you heard this? You have to test. You have to try alternatives and see what really works best for you, on your pages, with your content and your visitors. Test, test, test some more. Track your results, analyze them, try variations. Too many of us don't test. We hear the mantra, but we don't do the work.
First, let's see if we can get an idea about location. (The graphic is included in the article on my site or you can take a look at it at the Google link included below) Generally, above the fold, at the top center of your content, below top navigation is the hottest location. Not immediately below which is good but not quite as hot. In a left sidebar, to the immediate left of primary content or below the primary content are also good. Most other locations are generally cooler.
Again, you need to test and you need to consider your users behavior - and their behavior may vary on different pages with different kinds of content. Google suggests that in some cases, such as articles, the best location can be at the end of the article. To quote Google, "It's almost as if users finish reading and ask themselves, What can I do next?" Well targeted relevant ads right there can provide the answer.
Don't blindly assume that sticking a nice big rectangle in the center above the fold will do it. It may, but depending on your content, it may annoy or inconvenience your users.
Users tend to focus on content, navigation and to a lesser extent graphics. Positioning your ads near these elements will often work well -- if those ads are targeted to your visitors needs.
The top three performers among the Google ad formats are the 336X280 large rectangle, the 300X250 inline rectangle and the 160X600 wide skyscraper. Google reports that the wider formats tend to do better than the taller ones. One reason may be that these are, perhaps, easier to read since they have fewer line breaks and require less eye movement. But, you need to use formats that fit your pages well. Once again, you need to test, but redoing your pages to suit a particular ad format may not be a reasonable alternative and you may discover that a different format actually gets better results.
Now we come to color. Conventional wisdom says that colors which tend to blend into your content do better. Some go so far as to suggest that colors which make the ads look like part of the content are best. Personally, I think anybody really believes those ads are anything but ads, but who knows. Google suggests that you may find that colors that standout from your content do better - or maybe the opposite. This is absolutely an area where you need to test alternative color schemes. Going with the conventional wisdom usually works fairly well, but without testing you could be leaving a lot of money on the table.
Google allows you to have up to three ad units and one link unit on your pages. If you have long pages with lots of text, can only use small ad units or are in a niche with a large ad inventory, multiple units can pay off. Keep in mind that the way ad serving works is that the higher value ads are delivered to the first ad unit block encountered in your code. Always make sure that this first ad unit is displayed in the best location (yeah - test). You want the higher paying ads to be in the prime hot location on your page. Weaker locations can get the lower priced ads. And if none are available, then nothing will display unless you've included an alternate ad URL in your Google code. To maximize monetization you should be including alternate ad URLs, especially if you are putting multiple units on a page. The use of an alternate ad URL also eliminates the possibility of being served PSAs (Public Service Announcements). It's your real estate, maximize your returns.
Nothing here is secret. Except for using the alternate ad URL, all of this information is available from Google's Optimization Tips page - http://www.google.com/support/adsense/bin/static.py?page=tips.html . You can buy books and courses, visit a dozen forums and, in the end it comes down to what your visitors do on your site. The best you can get is general guidance. This means averaged outcomes over many sites, many types of content. If you are serious about doing whatever you can to really optimize your AdSense returns, there is only one thing to do - test. Whether it's AdSense, opt-ins, copy, headlines - anything with a measurable outcome that you can track - then the way to improve is to test and keep on testing.