Here's what I use, with Portable Keyboard Layout by Farkas Máté (AHK-based):
; These keys are modified/transposed by holding down the 'extend key' (CapsLock by default):
;+------+------+------+------+------+------+------+------+------+------+------+------+------+
;|Esc + |F1 <> |F2 << |F3 >> |F4 <> |F5 <> |F6 << |F7 >> |F8 <> |F9 <> |F10<> |F11<> |F12<> |
;| Caps | Play | Prev | Next | Stop | Mute | Vol- | Vol+ | Media| BrHom| Mail | App1 | App2 |
;+======+======+======+======+======+======+======+======+======+======+======+======+======+
;|` ¤¤¤ |1 |2 |3 |4 |5 |6 |7 |8 |9 |0 |- |= |
;| Del | F1 | F2 | F3 | F4 | F5 | F6 | F7 | F8 | F9 | F10 | F11 | F12 |
;+------+------+------+------+------+------+------+------+------+------+------+------+------+
;|Tab |Q ¤¤¤ |W *** |F <<> |P <>> |G *** |J ### |L ### |U ### |Y ### |; ¤¤¤ |[ ¤¤¤ |] ¤¤¤ |
;| | Esc | *WhUp| BrBck| BrFwd| *Btn1| PgUp | Home | Up | End | Del | Esc | Ins |
;+------+------+------+------+------+------+------+------+------+------+------+------+------+
;|Caps+ |A +++ |R *** |S +++ |T +++ |D *** |H ### |N ### |E ### |I ### |O ¤¤¤ |' ¤¤¤ |\ ><> |
;| ++++ | Alt | *WhDn| Shift| Ctrl | *Up17| PgDn | Left | Down | Right| Back | Apps | BrFav|
;+------+------+------+------+------+------+------+------+------+------+------+------+------+
;|Z ¤¤¤ |X === |C === |V === |B *** |_ *** |K *** |M *** |, *** |. *** |/ *** |Spc ¤ |Entr¤ |
;| Undo | Cut | Copy | Paste| *Le17| *Dn17| *Ri17| *Btn3| *WhLe| *WhRi| *Btn2| Enter| Break|
;+------+------+------+------+------+------+------+------+------+------+------+-------------+
;Legend: # Movement; + Modifiers; = GUI edit; * Mouse; <> MultiMedia; ¤ Various commands.
As you can see, F1-F4 serve the Player buttons (works with most players, just like the Media Keyboard keys do), F5-F7 are sound control, and F8-F12 are for starting apps. There's also a Favorites key, wheel scrolling and other navigation there. Other functionality is generally included passively, such as Extend-'5' for Refresh.
Works great for me, at least! Tell me if you're interested, or look it up on the Autohotkey forums.