Most of them are little things. Stuff that might not even come up, though some of it will. They tend to fall into two categories: stuff without rules and stuff that's different enough to give one pause.
Essentially, as with any d20 game, look up the rules in a place or three when you need to know them, just to make sure you're using the correct rules.
Without rules: non-lethal damage with normally lethal weapons; recovery checks for intelligent undead; judging encounter difficulty; creating magical items (there are actually three different rules in various supplements but all have different assumptions and goals), thankfully magical items are totally optional.
Different: undead casters; the incredible power of scaling damage; the knowledge categories; the lack of a Profession skill (impact varies from table to table); three levels of fatigue; repeated power usage; damage resolution; the defensive nature of the rules.
There are others, varrying from person to person, but those are the ones that stick out in my mind. None of them, to me, are deal-breakers.
The freedom, and options the rules provide, both in generation and in play, really let characters feel heroic from first level. The options of Conviction are powerful and numerous. Less sexy, but just as impressive, are the options of Extra Effort. These two mechanics, as well as the fact that every effect is resolved with a saving throw, allow characters of any level to be cinematically heroic and capable in a world that is all too dangerous. Or not.
Minion rules take a few minutes (no more than ten) to grok, but provide the Narrator with a wealth of story-telling options to resolve encounters. They let a small army be a fair challenge, easily run. They reduce the utility of miniatures and battlemats, by reducing the lingering presence of foes.
