Step 1: Find your tone
Find a guitar tone that you really like. Turn off all reverb and effects at this stage. When you have your perfect tone ready for recording, roll back on the gain slightly. The reason I do this is because when you start to record multiple layers, the sound becomes more saturated. So your ideal tone will probably sound too smooth and fuzzy if you layer it. This is the tone I have chosen for this demonstration:
Step 2: Prepare to record
Have a drum track ready to record over. Make sure your guitar is perfectly in tune. If the guitar is even slightly out, the tone won't sound good. You may not even notice it sounding out of tune, it just won't have that sweet crunch that you get from distortion. Tuning also goes for intonation. If the intonation of your guitar is slightly out, you may want to temporarily tune in-between to compensate.
If you're recording with a mic, make sure to use headphones so that you don't get any significant signal bleeding. When using microphones I also recommend enclosing the cab in a non-reflective area. For example I used to hang some sheets over a chair and over the cab, with the microphone inside. This stops room reverb that may cause a muddy tone that lacks "presence".
Step 3: Record
It's important when you record that you play as tightly as possible, as you're going to be using multiple layers. If each take is not perfectly in time and played cleanly, the layers will not gell - you'll clearly hear two seperate layers, which will sound messy. The goal is to give an impression of a huge sound, but not make the listener think they're listening to many different guitars.
Start by recording just two layers, the exact same riff twice. Pan them 100% left and right. The reason for this is that the small differences between the two recordings give it a wide stereo image and make it sound bigger.
Step 4: Tweak, re-record
If you picked a suitable tone and played it well, this should already sound good. But the chances are that in listening to both layers together it won't sound perfect, and hopefully you'll be able to put your finger on why, and tweak it out. I often alter the gain and eq on the amp or amp model.
This is what it sounds like so far:Step 5: Make it huge?
If you want an even bigger sound, there are a few things you can try. I personally don't like using more than one layer on each side, as phase cancelation can ruin the tone, and take away from the sound rather than make it sound bigger. However, some people like this sound. If you add another layer down the middle, then send the 3 tracks to their own bus (explained in the next step) - you can use a stereo expansion effect to make the sound even bigger. Be careful with this technique as it can have some weird psycho-acoustic effects and should be used in moderation. This is what 4 layers sound like, 2 layers have a stereo widening effect applied while the others are panned but not widened.
Step 6: Track effects
Send the tracks to the same bus
If your editing sofware is capable, it's a good idea to create a "bus" track. This enables you to send the guitar tracks through a single effects chain, so you can change volume, eq, stereo expansion etc. on the entire mix of guitars at once.
EQ
I usually reduce the low bass from ~80hz down by 5-10db. 
This will lead to a
tighter sound when there is bass in the mix. This is the only eq that I regularly apply, the rest is down to judgement.
I'd wait until the music is near complete before adjusting this, as it will
depend on the other instruments around it - you may have all the space for the
guitar, or you may have to fit vocals and leads over the top.
Reverb
I don't usually use much reverb, but it can be useful if you want the guitars more in the backround, or if you want to add "air" to the mix to make it sound smoother. For this I use a reverb effect that allows me to accurately control the EQ of the reverb, and I make it mainly 8-16khz.
It really depends on the tone of your guitar. If it has an awkward "in your face" presence, experiment with reverb. Be careful not to let it take away your stereo width, as some plugins will do reverb based on both channels and convert it to mono.
Step 7: Mixing...
Here's what my favoured 2 layer approach sounds like with bass:
