The donor for my engine swap was a 97 K2500 Suburban that had a 454/4L80/NP241. It had 288,000 miles on it and the still pulled fine. It had a 14BFF with 4.10's and cruised like a dream on the highway with no issues. With a 4L80, it has a 2.48:1 first gear and a .75:1 OD. It cruised at 2000rpm at 60 and 2500rpm at 75mph, which is right in the powerband you want it at without compromising fuel mileage or longevity too much. The equivalent first gear ratio of a 2.48:1 first gear and 4.10 axle is 10.16:1.
With a 465, you have a 6.55:1 first gear! So the equivalent first gear starting ratio would allow you to have a 1.55:1 axle ratio! That's insane! No one in the world would say that a 454/4L80 doesn't have enough grunt towing with 4.10 gears. In order to get the equivalent OD ratio as a 4l80, you would need to go down to 3.05 gears. With 3.05:1 rear gears on the 465 you would get a 29.90:1 final ratio(DOUBLE the overall gear ratio of a 4l80 in 1st), a 10.9:1 ratio in 2nd(still more than a 4l80 in 1st) and then the 3.05 ratio in 4th. That would put you at the same 2000rpm at 60 in 4th and 2500rpm at 75mph. That would be the mathematical equivalent(pretty close) of having 3.90 gear and the gear vendors activated. All of these RPM numbers are with 31" tires, so bigger tires would also adjust this RPM down. So say a 35" tire with 3.42's would give you the same final RPMS.
So, if your main concern is being able to tow 10k lbs and still keep reasonable highway mileage without having to change too much... you could gear very low and take advantage of the super deep gears on the 465. A high rear gear with the gear vendors will give you the same final ratio in OD, but you will basically never use 1st gear, because it is just stupid low. With 4.10s, a 31" tire, and assuming the 454 is all done by about 4500rpm.. you are shifting out of 1st at 15mph.
With the 3.05 gears, you would get 1st gear to run out to 20mph, 2nd would then run out to 38mph, 3rd revs out at 80mph, and 4th becomes the cruising/highway gear.