Small weapons become useless. Two handed weapon wielders in heavy armor rule the field. You may or may not like this. I found that it really restricted choice in character concept in a way that I didn't like. Sometimes there can be too much realism...
Monks also don't work anymore at the lower levels.
I'm going to be running an oriental adventures campaign using the Grim and Gritty rules system. If it doesn't work out we'll change back over to regular. Maybe I'll post how it works out.
I tried them for a 1-shot classless cyberpunk thingummy . . . it was pretty cool. But, although the players said they had fun, they preferred VP/WP to GnG.