Top three:
Toyota 2JZ series
Ford Australia's Barra 4.0L Turbo
BMW S54 coming in just behind those two, IMO, because of the 'all or nothing' nature of upgrading it, as well as the huge price tag attached to the 'all' option.
The Barra 4.0T is better known as the Falcon XR6T engine. It's a 24v DOHC inline 6 with a Garrett GT35R from the factory. The earlier ones made ~320hp stock, now they're ~415hp off the showroom floor. With a factory GT35R and a 4.0L displacement, it responds to modifications even better than a 2JZ-GTE on stock twins. Plenty of them in 1200+hp big build 2JZ-GTE territory, too. In the turbo inline 6 game of easy mods, massive power and great reliability, it's the 2JZ-GTE's only true competition IMO.
If only Ford had brought them here and put 'em in a Mustang or something... sigh
The S54 has the reliability part hammered down, but getting to big power is a massive expense for both the hard parts required as well as the tuning.
The RB26 is awesome in it's own right, but requires extensive reinforcement of the oiling system, cooling system, etc before pushing over 450-550 reliably - very respectable from a throttle response & exhaust note standpoint, but she just isn't the prettiest girl at the dance once a 2JZ or Barra 4.0T strut on in.
For classic sports inline 6 engines, I have to agree with Nick on the 4.2L E-Type. My personal soft spot is for the 3.4L though, since my grandmother had a '51 XK120 when I was a wee lad. It was pearl white with a crushed red velvet interior and a polished rosewood dash and was just unbelievably fancy compared to my Mom's Volvo 244DL. The original 3.4L engine ended up having fatal problems, so it was cleaned up to look pretty and put on a stand in the waiting area of the workshop that cared for her XK120. A more powerful and easily repaired replacement engine was sourced from some later year XJ sedan. My family wasn't very car-oriented back then so the details are lost to the mists of time. My uncle ended up selling the XK120 to the shop that cared for it when she passed, I was only 7 or 8 years old at the time.
If I ever hit Powerball, I *will* hunt down that XK120.
Other classic I-6's worth mentioning, IMO, are the Nissan DOHC S20 that made the GT-R nameplate what it is today, the Toyota 3M-G that would become the grandfather of all Toyota DOHC engines, and of course the Z's L-series. Chrysler Australia also made a Hemi version of the straight-6.
If we start talking diesels, the CAT 3406 wins. Though the 12v Cummins is a bad mamma jamma when it comes to diesels.