Since this isn't in the classic long-hood section of the forum, I will weigh in.
I have driven CAT 3406E, Detroit S60 and Cummins ISX. I can't speak about other engines, but this is my take:
The CAT can pull and does well if you don't mind spending money on fuel. It was not designed for fuel economy and anybody who claims they get more than 6.5 with one under normal working conditions will get a long, hard side-eye from me. They are expensive to maintain, but if properly maintained, will give you lots of good service. The problem comes in when guys try to soop them up beyond their internal capabilities. Sure, you can get 800 hp out of them ...for about 500K miles, then you're looking at an (expensive) in-frame. CAT got out of the highway business for a reason. They could not deliver the demands from the government.
Detroit S60 was a great, reliable, well-designed engine. Then, they started adding emissions stuff to it and ruined it. It was easy to get 7.5 mpg out of a pre-EGR S60 and climb hills well under heavy loads. It almost seemed like the heavier the load, the better it would climb. It was doggy at the low end, but did well on the highway. Maintenance and repair was less expensive than CAT. Overall, a decent engine for what it was. It was specifically designed for large fleet operations, although, as
@mndriver will tell you, it's a good choice for small operations, too. But it was not designed for emissions control systems. Period.
Cummins ISX was designed to accept emissions control systems while delivering adequate power and exceptional fuel economy. I was getting low 8s with the last one I had and able to repectably pull hills at the same time. I wasn't impressed with the engine brake, but knowing that, I just didn't fly down hills. It will last a great long time as long as it is properly maintained. If you fail to fix a problem until it stops you on the side of the road, it will cost you a lot of money. But if you fix it when you notice it, repairs and maintenance are reasonable. With this engine, maintenance cannot be stressed enough. However, in the long run, it will cost less in overall maintenance outlay, both in time and in money spent, than either CAT or Detroit. An inframe on this is more than a Detroit, but you can get a longer average service life out of it. (Unless you're MND, who can pull over a million miles out of a S60...that's why I said average.)
Of the three, if I was to choose, it would be the Cummins ISX 435. It has the best balance of power, fuel economy and maintenance cost.
This is an opinion. Take it for what it's worth: Pampers-filler.