The Gen 4 has an initially smaller grip than the Gen3, and comes with two different backstraps to adjust the grip to your liking. Most seem to prefer no backstraps. The 1st backstrap makes the grip the same size as a Gen 3 gun and the second one makes it a bit larger. This is the one I actually prefer on my G19 so far.
Next, the recoil spring has gone from a single spring to a dual spring setup to lessen the felt recoil and to reduce stress on the frames in .40 guns and above. Theoretically, Glock .40 pistols were guns adapted from 9mm. Now the theory is the Gen4's were designed more around the .40 cartridge. This originally caused issues with the new 9mm variations of the Gen 4's due to the fact that they tried to use the same spring for both, making the 9mm's only truly reliable with the higher energy 9mm rounds out there and made them highly susceptible to limp-wristing.
Another change is the grip surface. It has a new, more aggressive gripping surface to make the guns easier to hold onto with sweaty hands or worse. It works quite well but can be a bit abrasive if you use an IWB holster. I also believe the finger grooves are a little less aggressive than the original finger grooves.
Last but not least, Gen4's have a larger mag release that is now also reversible.
Known issues initially with the Gen 4's include, unreliable cycling with the early 9mm's due to being over sprung. Eventually this was fixed by offering a spring exchange program that eventually delivered the proper spring to those affected. Also a problem were bad extractors. this issue was not limited to Gen 4's. It had to do with a design change that was made to both Gen3 and Gen 4 extractors. Don't quite remember what the issue there was.