SONAR from Cakewalk takes a bit of beating methinks (Although it is a tad expensive) MIDI and audio integrate seamlessly and the bus routing has been improved beyond recognition in the latest version 8.
e.g. you only need one instance of say, a reverb effect and you can apply as much or as little of the effect to individual tracks. Principle advantage of this method is that it takes the strain off yer processor thus allowing yer mixes to contain LOTS of soft synths and effects etc. If you do overload the processor there is an option to 'freeze' any soft synth tracks you have by bouncing same down to audio thus freeing up the CPU for additional tracks.
I have used most of the MIDI/audio sequencers out there at one time and can honestly say SONAR is probably the most 'musician friendly' one to date. After sales support from the company is pretty damn nifty and there is a very active forum of users on the website that are extremely helpful (and show you how to do things that are sometimes not documented in the manual)
Disclaimer: I have never worked for, dated anyone from, played tennis with or performed babysitting duties for any employees of the Cakewalk company.