First, would anyone hesitate to buy one of these things used? Are the generally reliable?

Second, is there a big difference in sound quality (effects & amp simulation) between the 300, 400, and 500 series?
Buy away. Good, solid stuff.

With ANY of this kind of gear, purchased used, it's mostly the mechanical stuff that will give you fits. Try the switches, check the connectors, check the expression pedal for smooth operation, listen for scratchy pots.

Yes, there are differences. I'd suggest ignoring the 300 and 400. Stick with the 500 or 500X, or pick up the Pod HD and add an FBV Shortboard later if it's a money issue.
Last edited by dspellman at Oct 10, 2014,
Personally I prefer the Zoom G5, but thats just preference. There's nothing wrong with the PODs
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I'd agree that if you can you should get the HD500. More memory for bigger effects chains if you need it.

My HD500 has worked great for me.
I bought the HD300 back when it was new and I really regret not going the extra $200 for the HD500, so I'd say if you're serious about purchasing a multi effect pedal go for the 500 (I think its called 500x now or something like that).

On the positive side, the HD300 has brought me wonders of joy, since my family hates amps (lousy acoustic inside my home), only issue I have is that the pedal is a bit hard to use, since it requieres a really hard stomp to change uses (volume/wah/whammy), but everything is perfect for me.
I've been impressed with my POD HD desktop which I use for all my guitar tones during recordings (see links in the signature if you want to get a tone example) the tones and effects available are versatile and some of the new amp simulations such as the Soldano, Mesa Triple Rec and Bogner are great following the latest firmware update.

Reliability wise, I've never had any issues and the Fbv is solidly built. The switches/expression pedal feel good quality and the wah sounds great. This is a link to Ola Englunds metal test of the POD hd500x.