Depends on the level:
ser and estar
preterite vs. imperfect
por vs. para
placement of indirect and direct object pronouns
But if you focus on the positive, Spanish is a relatively easy language for English speakers. There are hundreds of cognate words (almost the same in both languages) because we share a common linguistic parent, Latin.
Also Spanish is so much more phonetic because there is only one vowel sound for each vowel, and most letters have only one sound. I have a dyslexic student who was originally intimidated about studying a foreign language, but he's doing great!