If by "muddy," you mean there's too much low end, I'd try out Geekydaddy's Mid Focus EQ suggestion above. Also, assuming you've updated to the lasest HD500 firmware, you'll want to play around with the new Cab Deep Edit Parameters. I'd suggest starting by finding those settings (in the amp/cab section) and increasing the Low Cut parameter up to around 100-120 Hz.

Even though the guitar has note fundamentals down to about 80 Hz in standard tuning, the Low Cut is a very gentle slope (you can see it here http://www.youtube.com/watch?v=53MtkBSRXT0 ). So, if you set it at 80 Hz, it will only bring down 80 Hz by about 3 dB. Setting it up a bit higher at 100, 120, or even as high as 200 or more (depending on the specific cab and the tone of the kick drum and bass you're playing / recording with) might be necessary to get rid of the mud.

1) are you using an amp model on the Pod?

2) if so, which one?

3) are you going for a distorted tone?

4) which pickup are you using?

I would look out for 2 things in your patches:

1) too much bass/dark signal going into a distortion effect or amp model using distortion.  sometimes just sucking out a touch of bass before distortion gets the tone less fuzzy and poorly defined and makes it clean and smooth.  your distortion should compress the bass, so it's not like your patch won't have bass.  and if needs be you can EQ it in on your amp, cab DEP's, or with a post-amp EQ effect.

http://foobazaar.com/podhd/toneGuide/ampTone#distortionType

2) you have unwanted clipping somewhere in the chain it shouldn't be.  sometimes EQ effects will easily clip.  Or if you're boosting beyond 50% in the amp block it can push it to clipping.  Turn off the parts of your chain that provide distortion and make sure you get a clean signal with them turned off.  add everything in one-by-one saving the amp block for last, trying to determine if anything's adding unwanted clipping. here's a guide on this subject:

http://foobazaar.com/podhd/toneGuide/troubleshooting#clipping

also, if you are using Input 1: Guitar, Input 2: Guitar/Same, this may lead to a slight phasing sound depending on how your patch is set up.  If you are using a single amp patch, try putting everything in Channel A - nothing before the path split and nothing after the Mixer.  In the mixer, set channel B all the way down to mute and pan channel A to center.  if you use stereo effects, this won't effect them - each channel is stereo.

if you're using a dual amp patch, try Input 2: Variax, then put a mono-summing effect before the path split.  For a complete tone-neutral effect, use the Noise Gate and set Threshold to min and Delay to max.  Otherwise, if you're using a Distortion effect, just make sure it's before the path split.

http://foobazaar.com/podhd/toneGuide/setup#input

I too had the same problem "issues with low end" through studio monitors and amp.

I followed geekdaddy's advice :- and now have amazing results.

I was considering going down the DT25 combo route, £550, Glad I didnt as my Peavey Vypyr 30 modeling amp (£150) using TWN or DLX amp settings sounds the best it ever has my USA strat now sounds like a Strat with lovely rich low end the goes right through you... fantastic !! . (Just need someone who can play it )

So thanks geekdaddy, and this may be a poor mans soloution to the problem of good tone