The hardest part of an I-601 or I-601A waiver is demonstrating extreme hardship to a qualifying US relative. The hardship has to be signficantly greater than the ordinary hardship that results from a family member being removed. Ordinary hardship may include diminished economic and educational opportunities. Ordinary hardship is not enough.

The hardship standard for the I-601 and I-601A are identical. The important difference is that the I-601 applicant must apply from outside of the United States and must demonstrate extreme hardship to a US citizen or permanent resident spouse or parent and the I-601A applicant may apply from inside of the United States and must demonstrate extreme hardship to a US citizen spouse or parent. USCIS will not consider evidence of hardship to US citizen or permanent resident children unless it is explained in a way that demonstrates that it effectively a hardship to the qualifying relative.

There is no limit to the number of I-601 and I-601A applications a person can file.  But waiver applications take time and money, so it's wise to carefully prepare the application.