To solve the expression ( 321 - \frac{53}{4} \times 675 \times (65 \times 4) ), follow the order of operations (PEMDAS/BODMAS).

Calculate ( 65 \times 4 ):
[
65 \times 4 = 260
]

Now substitute into the expression:
[
321 - \frac{53}{4} \times 675 \times 260
]

Calculate ( \frac{53}{4} ):
[
\frac{53}{4} = 13.25
]

Now multiply ( 13.25 ) by ( 675 ):
[
13.25 \times 675 = 8937.5
]

Now multiply ( 8937.5 ) by ( 260 ):
[
8937.5 \times 260 = 2324350
]

Finally, subtract this result from ( 321 ):
[
321 - 2324350 = -2320319
]

Therefore, the result of ( 321 - \frac{53}{4} \times 675 \times (65 \times 4) ) is (-2320319).

Thus the final answer is:
[
\boxed{-2320319}
]