One is the location of the red/yellow/green titlebar buttons. Like FF, Safari eschews a traditional titlebar and puts those buttons level with the main browser chrome. (IMHO I think this is a good trade-off to make for a browser; I'm not complaining)
Two is Safari's scrolling behavior. It seems to use its own scrolling behavior, separate from the standard scrolling behavior provided by MacOS. I've tried a few apps that modify system-wide scrolling behavior, and they work everywhere but Safari. They make Safari's scrolling insanely twitchy, with a single click of the mousewheel causing Safari to scroll 10x or 100x faster than anything else on the system.