Well I suppose the main problem is the lack of space. You have to cram all those sockets into the standard ATX format.
As far as problems using a mobo, the BIOS is what gives a lot of people grief. This is a little bit of memory (powered by a battery on the mobo) that contains enough instructions to initialise the mobo. If your BIOS gets corrupted somehow you're pretty much stuffed (you can replace the chip but finding one can be hard). There's a new system called EFI that will replace BIOS eventually.
Other problems basically revolve around obsolescence. You buy a mobo that takes a certain series of CPU or GPU, then they invent a new type of socket and you have to replace your mobo to upgrade.
Obviously there's heaps more problems than this, just ask google.
Yep another common problems with mobo is they just die on you which could be defined as fried during normal working. THis is when certain component on the mobo itself fails like the capacitors etc. Can be tricky to find out what caused the problem but something like that would mean that you have to brace yourself for the bad news and dish out for new one most likely.