Improvements against scrypt for the birthdayhash will help a bit, but like you said any tricks generally translate fine into ASICs.
For your example, since the mac pro has 16 times more RAM and hashing power it will be exactly 16^2 or 256 times better. Well worth the 50x cost. Since this is quadratic it will just get worse when you get into 128GB servers.
I like the elegance of having the RAM be the main resource for hashing, but I think we have a ways to go before making it practical. I'll keep thinking about it.
Nathaniel
The problem with memory is that setups will then turn to server motherboards, some of which can hold an insane amount of RAM. http://www.newegg.com/Product/Product.aspx?Item=N82E16813182346 This motherboard has 24 Ram Slots for $490.00
For best value, we can go with 16gb memory sticks at $150.00 each also available on newegg. http://www.newegg.com/Product/Product.aspx?Item=N82E16820226412
With 24 of these, you would have 384gb of Ram. Granted, your cost would be ~$6000 when you finally put the system together. However, with 384gb of ram, this system is 144 times as good as your Mac Pro for around 1.2x the cost. People would just have systems like this lying around.
Also, that doesn't even count one of Intel's Server Motherboards which can hold theoretically up to 1.5TB of ram (48 slots at 32gb each). However, at current prices your looking at 30 grand just in ram for that.
However, that being said, I would support a memory based coin. I kind of like the idea of having my house covered with servers each having hundreds of gb of ram versus the idea of my house covered with Asics .