I'm interested in what others have to say about this too - I'm not a guru or anything like that, but I've got a mental list that I go over before I consider a Mileage Run - in no particular order:
1) Can I do it so the EQM cost is around 2 cents?
2) Will this MR be the most cost effective way for me to get the miles that I want or need? (i.e. should I book one now, or should I wait and see if fares get even lower in a few months? Unless it's an amazing deal, like a lot of the ones found here, I'll probably wait if I know that NW's going to roll out a big promo like FFF4 or if UA's going to offer double EQM's for 100 bucks)
3) Will I have to overnight (I've only booked one run where I haven't overnighted - but it'll be a day in PHX in September - 18.5K total US miles for 200 bucks - this run wasn't for EQMs, but seemed like the cheapest way to top off my account to a usable level)? What will the cost be - airport bench or hotel? For example, if I went to NY on a run, I wouldn't want to have a long overnight because I'm sure the cost of a hotel would be way more than I'd want to pay, but if I could do a quick turnaround on a redeye, I wouldn't mind as much. If I do need a hotel, I see if any of my friends want to go to drop the cost down.
4) Is it somewhere I'd be interested in going if I have to overnight? Not that I'm picky about where I go, but if I have to spend the night, I'd rather do something than just sit in a hotel & watch TV.
5) In terms of routing, are all the connections doable within the enough time? Would this particular run which happens to connect in, for example, MSP & ANC & SEA probably be a better idea to schedule for the summer instead of the winter given the uncertainty of weather (I've had weather delays on a MR before & I lost out on 2 connections because the next available flight back home was direct from MSP)
6) Will someone be able to watch my dog?
7) I check Webflyer's Bonus Promotions page.
8) I ask on FT if I've got the best possible routing & hope that someone smarter than me replies. (And they do - thanks, guys!)
9) I ask myself - is this REALLY worth the money I'm about to spend? And sometimes, even on a good fare, it's not.
10) As for bumps, I have certain airports & times that I feel lucky on, so I try to route through at those times - and thanks to a tip from Viajero Joven, I carry a list of alternative flights with me.
11) I try to make sure I'm on the right airline's metal (as a NW elite, there are times that I wouldn't want to do a transcon on CO metal if I was only getting 50% of the EQMs - on DL metal, I get the EQMs, but not the upgrade possibility).
12) I try to get on bigger planes if possible - more opportunities for bumps & FC upgrades.
13) I remember that to err is human & misconnects & weather happens, so I make sure I relax - I'll always get home eventually & worse case scenario, I use another day of vacation.
14) I make sure my iPod mini (thanks, FT) is fully charged & I have fun.