When you say "USB" do you mean a USB-gamepad chip, or a USB-keyboard chip?
Obviously the I-Pac(tm) is a keyboard encoder, but people here have a bad habit of referring to things under a generic banner.
If it's a keyboard encoder, USB or PS/2 doesn't matter. Most systems will enable USB-PS/2 compatability within the motherboard's BIOS so that even DOS can take input from the encoder via USB. Linux 2.4/2.6, MacOSX and Windows 2000/XP will all handle USB keyboards natively.
If it's a USB joystick/gamepad encoder, that's a different story. DOS is out of the question here from the word go. MacOSX, Linux 2.6 and Win2k/XP are all fine from an OS/Kernel and MAME point of view, but you're going to have to check up on your frontend of choice to make sure it allows mappings from USB-joystick device inputs to the frontend. I know from personal experience that MAMEWah under Win2K/XP is fine, and so is AdvanceMenu under Win2K/XP and Linux 2.6. Anything else you're going to have to check for yourself, or hope that someone who has used/written them is kind enough to spot this thread and answer.
Performance wise, it doesn't matter squat. I know there have been massive fights in here between USB fans and PS/2 fans over whose encoder is 2ms faster than someone else's encoder, but at the end of the day it doesn't make any bloody difference to me playing on my 2-player cabs as to which I use, and I've tried various brands in various USB and PS/2 setups, and it all feels the same to me.