Which is better Ibanez S571DXQM or the Ibanez S421? What is their differences? Which has a better pickup?
The S571DXQM has a single coil pickup as well as 2 humbuckers like the S421. People who like the extra pickup say it's easier to emulate strat sounds in the 2nd and 4th switch positions, and like the larger range of tones you can get from the Hum-Sing-Hum setup. Those who don't like it say they don't need it, or that the single coil just gets in the way of their picking.

The S571DXQM also has a maple top and a nice transparent grey finish, where The S421 has just the mahogany body, and a blackberry sunburst (as well as a black finish that's discontinued but still around).

They both have Infinity pickups, which a lot of people find lacking. I think they're alright in my S320SP (22 fret version, with trem, 2 humbuckers and chameleon finish), but I don't get quite the chunky-heavy sound I like in the bridge for aggressive palm-muting. But the 5 way switch on it gets me a lot of varied tones.

All in all, It's really up to you. They're about the same level of quality I think. I don't have much experience with HSH S series, but I'm sure you'll be happy with either you choose.
S571 is HSH, the S421 is HH. Both mohogany body with maple 3pc wizard necks and rosewood boards. Pickups are the exact same INF pickups.

The only differences are the S571 has a quilt top, bound neck and a middle single coil pickup.