STEP ONE

Download Rainmeter.

I have only tested the 2.1 release, so I'm uncertain of any issues with the 2.2 Beta.

STEP TWO

Download the skin and backgrounds.

You can also download SpeedFan to enable the temperature gauge in the skin.
Also, mad credit to darkstaruav of DeviantART for creating this!

STEP THREE

Install Rainmeter

Pretty straightforward.

STEP FOUR

Install Mass Effect Theme

Browse to the location you downloaded the file to, unzip, and double click.
It really is that simple.

Now comes the fun part!
When you first start up Rainmeter, it will probably look similar to this:

STEP FIVE

"Unload" all illustro modules.

To do this, use the Rainmeter Manager to expand the illustro folder, then expand a module folder, such as "Clock", click on the corresponding .ini, then click "Unload" on the right pane.
Repeat for all loaded modules.

STEP SIX

Load all Mass Effect 2 modules.

In the Rainmeter Manager, expand the "Mass Effect 2" folder, then expand a folder such as "Bottom Bar." Click the .ini and hit "Load" in the right pane.
Note: Both Bottom Bar and Top Bar have multiple .ini's corresponding to different styles of bars. I'm using Concave.ini for the Bottom Bar and Top Bar Rounded.ini for the Top Bar. Feel free to experiment and use whatever you desire.

STEP SEVEN

Arrange your desktop.

Everything moves by dragging and dropping. Use the screenshot above as a guide for placement.

STEP EIGHT

Customize the Launcher module.

Simple hit "Edit" right on the module to bring up the text file.
Fill in the title of the Application where it reads "Application_x" and the path to the application right below.
For example, I filled it in with my Web Browsers and Steam.
Click File -> Save, then Refresh the module to see the changes.

STEP NINE

Customize the Weather module.

Browse to Weather.ini in the Rainmeter Manager and click Edit in the right pane.
Towards the start of the document, you'll find "Location=USXXXXXX".
To find your location code go weather.com and search for the name of your city. The Location code will be the set of letters and numbers at the end of the URL. [screenshot]
Also, change Metric=c to Metric=f if you'd like to see the values in Fahrenheit.

STEP TEN

(Optional) Customize Cerberus Daily News

Personally, I wanted a news feed that was more relevant, so I edited "Cerberus daily News.ini".
In the file, find "URL" and change this to the RSS feed of your choice.
On my screen, the box was also a bit unreadable so I also took the liberty of increasing the FONTSIZE to 7, changing the W (Width) to 500 and H (Height) to 50.
This meant I also had to change the spacing and recreate the hover graphics to keep it looking good.
It's a bit hard to explain here, but if you also find the box is a bit hard to read with original settings, I can make the files I customized available for you to download. Just ask on our forums or @ me on Twitter.

STEP ELEVEN

Set your wallpaper!

Hopefully you've done this without me needing to tell you... but if you haven't, do it now!

STEP TWELVE

Lock your modules to the desktop.

You may have noticed when clicking about in the Manager that there is a setting called "Position." By default, these are all set to normal for your loaded modules, but what we want is for these to be set to "On Desktop."
BUT THERE'S A BUG!
With the current build of Rainmeter, this setting isn't actually saved upon restart, but there is a way to FORCE it to.
Click on "Edit settings" at the very bottom of the window.
Scroll down to where the [Mass Effect 2\Modules] are listed.
Copy + Paste this:
AlwaysOnTop=-2
under every single header.
File->Save

STEP THIRTEEN

Grab a drink.

You deserve a little breather.

STEP FOURTEEN

Save the theme!

In the Manager, tab to "Themes."
Check the "Include current wallpaper" option, and think of a brilliant name.
I came up with "Mass Effect 2."
Hit save.