Yes but the options are what makes the POD more unique than a mere mimic of the amps in question. I tend to more use the uber gain amps which use a 4x12 and there is a dramatic response with the modeler EQ on any cab.

Just because a cab is a 4x12 does not mean it cannot have fairly flat response without artificial coloring (in the range of the guitar spectrum).

My last cabs I used, were loaded with JBL MIs and when pink noised it was nearly flat across the range of the guitar frequency range. My sound engineer brother was quite impressed that a "guitar cab speaker" could be so efficient without dramatic peaks and valleys in the guitar spectrum, they required just a couple moderate EQ adjustments on the 12 band I used to use before my power amp. (everything has a resonance frequency which multiplies in octaves, EQs serve to flatten out the overt resonance points-but only on a reference pink noise open analysis, there is a difference in EQ for tone weirdness and EQ for correct response reproduction. Ideally one wants the speaker or sound system to be able to reproduce the full range of frequency range but one seldom presents a flat response to the system in tones during live performance. )

My new cab is also properly dampened with material to eliminate hollow woofing and phase distortion that some cabs present as tone when basically being a hollow box. Some think a hollow cab is some of the tone, standing wave and phase distortion is not tone in the matter of sound engineering.

For my style of playing the 4x12 is what works the best for me. I have been a half stack player for many years and that is the rig that always delivers the goods for me in any application. I just do not like low wattage amps all that much, there is much more to wattage headroom than merely associating wattage with loudness. Loudness builds approximately 3db to a doubling of wattage which is not as much as many let on. 3db is the difference in volume between a pedal and a line level loop. A 100watt amp is 3db louder at peak than a 50watt and as well as the 100watt amp being perhaps 10db louder than a 10watt amp at peak.

The reason massive PA systems are so loud is the ratio of watts is so massive. a 1000 watts and you have a 100db in volume which is a whole "jet plane takeoff" lot. In the matter of guitar amps, for me cutting the wattage out of a guitar amp is cutting its balls off while not really lowering the volume all that much.

Points:

1) Wattage is not really about volume

2) Power tube distortion might be desirable for blues type or some fusion tones but for various metal level gains not a really good tone.

3.) A small speaker simply cannot reproduce the low end of a larger, it is just physics. 

And when I do use a 2x12 cab model the resulting EQ on the POD does brighten and open the sound. It does not sound like a typical 4x12 hooked up to a Fender twin. Sounds better actually, sort of like the best of both worlds, a bright and vibrant Fender with some more balls.

The problems w various speakers are problematic to the laws of physics regarding sound and frequency. Some things are what they are. A larger speaker manifests the ability to reproduce more low end than a smaller one. A closed cab by isolating the rear wave of the speaker phase is heavier and deeper resonance than an open back which allows the sound to breath and escape. "Airiness" can be approximated with EQ and ambience via the mic pre-ambience adjust or the basic reverbs.

Wattage is headroom, and on the POD one can use one of the smaller amps and get a great tone while piping it into a power amp which will not peak out on wattage like the real amp and can project the tone of the amp beyond the ability of the little amps. Overt power tube or power amp disortion while being the rave of little amp users, has limited tonal desirability in all ranges of musical styles. Little amps do that pony trick well but they tank out in wattage very early on. That may be what you want and that is all fine and good but do not expect that amp to reproduce an uber gain amp sound like the POD can do. 

Something to consider in the differences of using "fullrange" monitor speakers on the POD,verses a guitar cab like I use, is the matter of the sound is going to be split and fragmented through the speaker crossover circuits and further effected by phase time defraction effects of frequencies leaving the speaker and reaching the ear in different phase distortions. The problem is reduced by using a BBE unit properly set up to reduce the phase time distortion but basically on a monitor type speaker with a two way or three way speaker config the sound will be split whereas in the straight on 12" cab further using proper dampening and a tuned BBE unit the sound is more so true to what the real amps sound like. Believe me on my tuned and tweaked in Fenders and cleans you would not, just hearing it, presume it was not a twin 12 tone. Plus my cab is split stereo wired to L/R channels w 2x12 on each channel, the main 4x12 models are mixed to center.

Just hear to tell POD users and those not finding the merging to their normal guitar amp in mono or a 4 cable method, just does not work all that great or perhaps does not really expand their sound in the manner they imagined:

Being a long term player of somewhere around 35yrs I have been through it all from A to Z and I am here to just state that using a modeler sounds better through a straight on power amp. Most guitar amps have their own voice and tone and merely running the POD into the effect return on the amp models might work to a decent degree but if you have a great amp it is beyond me why you would want to do that.

If you want a more genuine realistic experimentation with amps in the POD you cannot afford; then allow the POD to reproduce them to their true potential.

Not running the HD500 in a stereo capable mode is not using half its ability. I would prefer separate cabs myself, and at some point I will get another one to get the speaker more far part which makes for more dramatic pan and spread effects.

I am just telling players 2 things about the HD PODs do not expect the POD to manifest the punch and power of the ENGL, Bogner, DualRec, Marshall, etc run through a tiny amp and do not judge the unit playing through a generic preset without tweaking, that is probably the most absurd thing I see on a daily basis.

I mean how hard is it to fathom that no preset anyone does, factory or user, is going to sound the same on everyone's guitar and amp much less their infinite touch and technique. Everything must be tweaked to one's environment EQ and rig. Seems to be a huge marketing crapola on presets and sounds-like click of a switch plug and play tones, any player of any experience knows that is a huge lark of nonsense.

By all means, everyone shoud use what that suits them and do what floats their boat as their guitar and style of playing is infinitely different. What works for one may not be the holy grail for another. Although my rig is very versatile and toneful to many different styles it may not be what someone else likes or can handle. if you're used to playing through a small low wattage single speaker amp with no pedals my rig would be too much to adjust to.

This post sort of wandered off from the basic topic but many things show up in the search enginers when one is looking for tips or info like I often do.

Just a note to anyone who might be reading things as I do to come across new ideas or tips on the POD:

I never had much luck getting the effect loop to sound right (which makes tying it into the amp a problem for me) I could not get some of the higher end pedals I have to merge with the unit as I had hoped in theory. So at this point, I just do not use the effect loop, some have realized you can program a nice clean boost by just jumpering the in/out and increasing the level for a switchable clean boost. That being said I run several of my better pedals IN FRONT of the POD and to report they work very well and the response of the POD to moderate overdrive, compression, and clean boost is the same as a real tube amp responds in gain and intensity.

I tend to hardly use any internal effects on amp in path except for my fav Pitch Glide harmonizer settings of 4ths and 5ths. I love the wahs, I find all the wahs in the POD to be really good. I set the output to about 92% on them and you have to select the right wah for the right amp and tone, not everything sounds right with anything. (Except perhaps a 5th up or down which sounds cool on cleans or heavy gain, I prefer the Pitch Glide harmonizer interval to the basic harmonizer effect as one does not have to maintain a strict boxed in key and scale.) Note: LINE 6 needs to fix the Pitch Glide Controller editor from percentage of pedal position to +/- interval like the pedal editor. One cannot set the expression pedal to an accurately tuned 4th or 5th (or any exact interval) like a real Whammy pedal.

Also another great tip to get a free volume pedal without having to use an effect block is to set the amp volume on a expression pedal where max would be where you would run the amp at peak, presto volume pedal without using up DSP on the effects blocks.

Also again that Mission L6-1 expession pedal made for the POD units is superb and well worth the cost for an additional expression pedal. I put all my wahs on that pedal as it feels and is just like a heavy duty wah chasis.

Any way just tossing out some tips and points for any who might pick up a piece of something that might help their efforts.