I use 5th gear in the S10 down to about 30mph or so to maintain speed or cruise. This is also my highest mpg window for this vehicle as well (55ish mpg in testing). No problem as long as you are not lugging it or putting a heavy load on the engine. When I encounter a hill or need to accelerate, I just shift into 4th (or 3rd if the incline warrants it) until I can shift back into 5th.
Engine is fine (including oil pressure) at 157,000 miles. I did torch a transmission last year, but I'm sure towing a trailer, at or slightly beyond the recommended tow weight for thousands of miles, and my wife learning to drive a manual were the culprit. Actually I'm 95% sure my wife was the culprit, but I would never tell her that.
Short answer, use 5th gear whenever possible...get better mileage.
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