一般说what's the trouble with you?/what's wrong with you?我从来没听过哪个外国人说what's your trouble的,那个意思就是"你有什么麻烦事吗"了.
最好还是用what's up或者what's the matter吧,比较地道,推荐第一个,这是在电影电视剧里听到最多的.