Ok, so that might seem a little vague. But when you think about it, everything wrong with Windows violates that definition.
The ideas outlined here were largely motivated by Raskin's book The Humane Interface: New Directions for Designing Interactive Systems. Note that some terminology on this page will be from this book, and while I will try to explain the basics behind it, I'd highly recommend reading the actual book to understand things fully--not only did reading this book make me think of user interfaces in a completely different way, it also made me think about how I used user interfaces in a completely different way.
As Raskin states in THI, there are two major problems with this:
It follows that it is in the best interests of a Windows user to set up their system such that the worst methods of completing a task (preferably, all but the best method) are inaccessible.
Fortunately, although Windows is extremely non-monotonous, it does give a fair amount of flexibility to allow the user to configure the environment to be more humane. However, this requires that the user know what constitutes a humane environment; also, in order to find the most effective way of completing a task, they must know all possible ways of completing it so that they can determine which is most humane.
Needless to say, this task is very difficult, and this document is aimed at finding the solution.
So, with that out of the way, let's see what we can do to make Windows a little more humane.
I'd sought for a long time to find better ways to start applications. Using the Start Menu, the Quick Launch Bar, shortcuts on the desktop, macro (shortcut) keys, and third-party utilities all had their major drawbacks.
It wasn't until several years of Windows use that I finally found the best launcher:

This seemingly innocuous little window has been a feature of Windows since 95, and when used properly, it's actually the fastest way to start any kind of application. The underlying concept is actually a very old one, of course: it's just a simplified version of the command-line interface from Unix and DOS, only it's more humane, if we set things up the right way. It also shares similarities with the excellent commands interface from The Humane Environment.
Here's how this works:
You're done! Now, to invoke any of your commands, just press Windows+R (the keyboard shortcut for the Run command), followed by the name of the command, and press return. For instance, using the 'mail' command example, activating your mail program would be as simple as typing Windows+R mail [return].
This method is faster and easier to habituate than any GUI-based solutions like the Start Menu or Quick Launch bar because you don't have to move your mouse at all, and it's also far easier to remember command names than obscure shortcut keys. It also provides more visibility than shortcut keys: if you ever forget what a command is, just type Windows+R commands [return] and you'll get a menu. You can make things more helpful if you set up the folder view properly. Here's mine:

Note also that the Run command is an excellent way to access directory windows: just specify the pathname, such as C:\stuff and a window to browse the folder will open. Newer versions of windows like XP will also attempt to auto-complete the file/directory name for you, which is helpful.
Finally, another reason this method is nice is because any keyboard shortcuts involving the Windows key aren't subject to modality: since no applications define Windows key shortcuts, typing Windows+R mail [return] is guaranteed to open your mail program and put it in the foreground, no matter what state your machine is in.
Using this interface to access much of the functionality of your computer will now let us do other things to simplify your Windows environment. As a general axiom, this is the procedure one should follow:
We will now put this philosophy to use.
After using lightweight Linux window managers like WindowMaker and Fluxbox for some time, I realized that the absence of a desktop isn't a flaw, but a feature.
What is the desktop useful for? There was a metaphor, in the beginning: our real-world desktop is where we get all our work done in real life, so it should have an analog in computer interfaces.
One of the major advantages of real-world desktops is that they're a place where we can put items we want quick access to: writing utensils, a nearby trash can, and so forth. But in the real world, we don't do things with keyboards and mice, and we can't have our mail magically appear and disappear in front of us with the tap of a few keys. Dragging a file to the trash can is no match for selecting a file and tapping the Delete key, and double-clicking on the "my computer" icon can't compete with pressing, say Windows+R mycomp [return]. Another major factor to take into account is the fact that the desktop is like a huge window that can't be resized or put above other windows, which means that most of the time you have to move windows out of the way or press keys like Windows+D in order to even make icons on the desktop visible.
It should also be noted that, like real-world desktops, computer desktops have a tendency to get cluttered. In fact, since all the advantages of having a computer desktop are nullified, it seems like the desktop only exists to get cluttered. This is especially the case with the recycle bin; whenever you put anything in it, its icon changes to a recycle bin with trash piled into it, which only makes the desktop look messier: in fact, whenever I deleted a file, I habitually emptied my recycle bin because I didn't want my desktop to look untidy. This, of course, completely defeated the purpose of having a recycle bin.
In fact, why does a computer even need to tell you that the recycle bin isn't empty? This may have been a pressing issue a decade or two ago when hard drive space was very limited, but in today's age of expansive hard drives, it makes more sense to keep the recycle bin hidden from view. This way all of the files you delete just stay in the recycle bin, so they're always available if you realize you want to undelete them; if you get low on disk space, you can just go into it and delete the largest files. This method will also result in less clutter in your system, since you won't ever feel afraid to delete files "just in case you need them later".
Ultimately, I was able to configure my Windows system so that all desktop icons and Start Menu features were removed; all such features were made accessible as commands through the Run window. Note that while much of this can be done through the standard Windows preferences and configuration settings, but some of them need to be changed using a tool like Microsoft's free Tweak UI PowerToy. Here is the result:

It should be noted, however, that when there are no permanent icons on the desktop, it can serve some useful purpose: namely, that anything put on it sticks out like a sore thumb. This means that the desktop is now a viable "staging ground" for temporary files, such as installer programs downloaded over the internet that should be deleted or moved somewhere after a first use. Thus the presence of any icons on the desktop serves as a reminder to delete them ASAP.
It follows that we should observe the following simple rule in regard to using the desktop:
For instance, here is my system tray:

The two computery icons tell me whether my wireless and LAN connection are working (of course, it sucks that I can't tell which is which from just looking); the speaker icon tells me whether my sound is on or mute, which is very helpful when I'm using my laptop in a public place; the icon to its right tells me that Norton Antivirus is working properly to protect my system; the padlock tells me that my PGP passphrases are not cached in system memory; and the plug icon tells me that my laptop is plugged into an AC power source and the battery is charging. The icon on the right, unfortunately, tells me nothing important--however, I need it because that's the only way to access the functionality of the tool it represents (probably a bad design choice).
We can thus intuit the following rule about the system tray:
One of the most common complaints I've heard about the Luna theme is that the titlebars of windows are far too large and waste precious screen real-estate; however, this can be remedied by going to Control Panel->Display->Appearance->Advanced, clicking on the titlebar and reducing the size from its default value of 25 to its minimum value of 20.
As such, this section really isn't so much about "humanizing" the Windows interface as it is just dealing with it.
So, here's a list of some shortcuts that you might find useful:
There may occasionally be situations where you need to repeat some specialized command that doesn't have a shortcut key but is available through the pulldown menu; in such cases, you can use the Alt key to select the command with the keyboard. For instance, in most programs pressing Alt+F will open the "File" menu, and pressing S after that will activate the "Save" command. In fact, such combinations can sometimes be easier to remember than shortcut keys themselves, although the fact that it's modal is a drawback.