Actually you can use a portable GPS during IFR operations, but only for situational awareness, not primary navigation. You have to file based on whatever other nav systems you have onboard, and use those systems for navigation.
The one practical limitation I can can think of is RAIM...portables don't have it. That is a requirement for GPS naviagtion. Also while some portables mount firmly, others just sit on bean-bags on the dash...not very stable in turbulence. Also the power cord might not have a reliable connection to a cigarette lighter plug.