i'm experiencing this problem myself. i have 2 servers, one using X86_64 kernel version 2.6.23-rc5 on a 100Mbit network and one with i386 kernel version 2.6.23-rc6 on a 1Gbit network.Yes, I have found that I get far less problem in this area leaving the MTU at 1500, then putting a larger MTU (usually 9000) into the routing table for segments, or even just machines, where I know there is direct connectivity. I use 9000 MTU with my directly connected file server, 1500 elsewhere. I can go to 9000 for nbd servers as well, assuming the connection doesn't pass a firewall.
They both have this issue with the sky2 network device driver whereby the device would stop working and need to be brought down and back up.
On the X86_64 kernel on a 100Mbit network, this is a very occasional thing, while on the i386 kernel on a 1Gbit network the device only works for a few minutes at a time. If i set the MTU to 7200 then the device seems to stay functional, but then i see long delays when it's talking to 100Mbit devices with standard 1500 MTU that are outside of its LAN segment.
This last might be an artifact caused by the firewall, i dunno.