I have come across renaming the first N column and last N columns.
Replace the value for N according to your need.
1) To Rename Last N Columns (ignoring the first 2)
cols_to_update = df.columns[:N].tolist() + ['col2_new','col3_new']
df.columns = cols_to_update
2) To Rename First N columns (ignoring Last N )
cols_to_update = ['col3_new','col4_new'] + df.columns[N:].tolist()
df.columns = cols_to_update
3) Rename Columns in the middle
cols_to_update = df.columns[:N].tolist() + ['col2_new','col3_new'] + df.columns[Y:].tolist()
df.columns = cols_to_update
4) To rename all columns - Make sure the list you assign is the same length as df.columns.
list = ['col1_new','col2_new', 'col3_new','col4_new']
df.columns = list
You can find more examples @ Multiple ways to Rename Columns in pandas