In addition to the "one way upgrade" issue, there is the "nonstop or connect" issue.

If you choose to upgrade in one direction, you clearly should choose to fly nonstop in that direction in order to get the longest BF segment. That is, unless you're not guaranteed an upgrade and want agonize about whether there will be a higher probability of availability out of EWR or out of IAH. In addition, you might be thinking that you may want to hedge your bet and pick the connection in IAH so you can at least get the Elite upgrade for part of the way.

On the coach half of your one-way upgrade (the non-upgrade half), you may want to connect in IAH or even LAX to maximize your Elite upgrade benefit. On the other hand, if this is the redeye, you may find it unbearable to wander around LAX at 5am after a 4.5 hour flight and may find prescription sleep aids a better choice.

Does anyone fly this route, you ask? The answer is... yes.

I usually fly this two or three times a year. Four times last year.